Wearable device for decreasing the respiratory effort of a sleeping subject

ABSTRACT

The present disclosure is in the field of sleep and respiratory care. In particular, the present disclosure provides means and methods for decreasing the respiratory effort of a sleeping subject. The present disclosure also provides means and methods for treating the snoring of a sleeping subject.

FIELD OF THE INVENTION

The present disclosure is in the field of sleep and respiratory care. Inparticular, the present disclosure provides means and methods fordecreasing the respiratory effort of a subject during sleep. The presentdisclosure also provides means and methods for treating the snoring of asubject during sleep.

BACKGROUND

Sleep disturbed breathing (SDB) marked with increased respiratory effortis a condition affecting sleep quality and causing excessive daytimesleepiness which contributes to most of road traffic accidents.

Continuous positive airway pressure (CPAP) is the most effectivetreatment for SDB; however, long-term adherence is limited. There is anurgent need for new therapeutic approaches and easy to use systems on alarge scale.

Electrical stimulation for the treatment of SDB occurring in the upperairways during sleep has been investigated. The genioglossus, which isthe constitutive muscle of the tongue, was considered like the maindilator muscle of the upper airway for specific targeting. Previoustrials aimed to target the tongue to move it to a more anterior positionin the oral cavity, either unilaterally or bilaterally for moresymmetrically movement of the tongue. It was confirmed that theunilateral stimulation of the tongue through an implantable stimulatorof the hypoglossal nerve may effectively decrease respiratory effort,but the related cost and invasiveness of the proposed treatment limitthe applicability to serious cases only. Bilateral stimulation of thetongue trying to provide more symmetric muscular tone to thegenioglossus and consequently to increase the upper airway patency morelargely and consistently has been proposed. Until now the preferredbilateral stimulation was examined with an implantable hypoglossal nervestimulating technology.

However, the anatomy of the upper airway in sapiens hominid is complex,as is the function, required for mastication, swallowing, speech andrespiration. Upper airway obstruction during sleep is more prevalentthan in other primates because the human pharynx has no rigid supportexcept at its cranial and caudal ends, where it is anchored to bone (inits upper side) and cartilage (larynx) caudally.

Therefore, the pharynx behaves in sleep like a collapsible tube duringthe process of respiration. On the other hand, most of the buildingmuscles of the pharynx anchor directly or indirectly via the hyoid boneto the mandible, the other mobile bone human beings have. Targeting onlythe genioglossus to prevent the occurrence of respiratory disturbances,such as airway obstruction or collapse, and related increase inrespiratory effort from the brainstem during sleep exposed to failurebecause pharynx can still collapse from other parts than the tongue.Indeed, until now, bilateral genioglossus stimulators could not exhibitsignificant physiological and clinical benefits in a large proportion ofpatients. There is therefore a need to remedy the issues and limitationsof state of art treatments for SDB marked with respiratory effort.

SUMMARY OF THE INVENTION

As described above, there is a need to remedy the issues and limitationsof state of art treatments for sleep disturbed breathing marked withrespiratory effort (SDB). The present disclosure relates to means andmethods for decreasing the respiratory effort of a sleeping subjectand/or prevent the occurrence of sleep respiratory disturbances. Inparticular, the present disclosure aims to provide transcutaneouselectrical stimulation to the masseter, pterygoid and/or temporalismuscles of a subject to adjust their contribution to the sleeprespiratory activity and reduce the subject's respiratory effort duringsleep.

Further, the present disclosure aims to provide means and methods forretraining the subject's brain through the provided electricalstimulation to decrease the central respiratory drive of the masseter,pterygoid and/or temporalis muscles.

An aspect of the present disclosure relates to a wearable device fordecreasing the respiratory effort of a subject during sleep, the devicecomprising:

-   -   at least one left electrode adapted to be positioned into        electrical contact with a selected portion of the subject's skin        ranging from a left masseter, pterygoid and/or temporalis muscle        motor point to a left posterior angle of the mandible;    -   at least one right electrode adapted to be positioned into        electrical contact with a selected portion of the subject's skin        ranging from a right masseter, pterygoid and/or temporalis        muscle motor point to a right posterior angle of the mandible;    -   a stimulator configured to apply a transcutaneous electrical        stimulation between the left electrode and at least one left        masseter, pterygoid and/or temporalis muscle and between the        right electrode and at least one right masseter, pterygoid        and/or temporalis muscle;    -   wherein the applied electrical stimulation promotes the        contraction of said left and right stimulated masseter,        pterygoid and/or temporalis muscles to controllably elevate the        subject's mandible such that the upper airway is opened.

An aspect of the present disclosure relates to a wearable device fordecreasing the respiratory effort of a subject during sleep, the devicecomprising:

-   -   at least one left bipolar electrode configured for mounting on a        selected portion of the subject's skin corresponding with the        position of at least one left target muscle including a left        masseter, a left pterygoid and/or a left temporalis muscle,    -   at least one right bipolar electrode configured for mounting on        a selected portion of the subject's skin corresponding with the        position of at least one right target muscle including a right        masseter, a right pterygoid and/or a right temporalis muscle,    -   wherein the bipolar electrodes comprise at least two        electrically conductive elements, wherein a first electrically        conductive element is configured for mounting on the target        muscle's motor point and a second electrically conductive        element is configured for mounting along the direction of the        target muscle fibre;    -   a stimulator configured to generate a biphasic transcutaneous        electrical stimulation to be applied between the two        electrically conductive elements of bipolar electrodes; wherein        said electrical stimulation promotes the contraction of the        target muscles to controllably elevate the subject's mandible so        that the respiratory effort can be decreased.

In an embodiment the electrical stimulation is a biphasic anddiscontinuous electrical current.

In an embodiment the electrical stimulation has a current intensity ofat least 1 mA to at most 50 mA, preferably 1 mA to 30 mA.

In an embodiment the electrical stimulation has a pulse frequency of atleast 1 Hz to at most 100 Hz, preferably 30 Hz to 50 Hz.

In an embodiment the electrical stimulation has a pulse width of atleast 100 μs to at most 400 μs, preferably 200 μs to 300 μs.

In an embodiment the electrical stimulation has a stimulation durationof at least 1 sec to at most 20 sec, preferably 5 sec to 10 sec.

In an embodiment the stimulator is configured to generate saidelectrical stimulation in accordance with at least one stimulationprogram, wherein said stimulation program is configured to generate anelectrical stimulation with a duty cycle that has a stimulation periodof 1 sec to 20 sec and/or a rest period of 1 sec to 20 sec.

In an embodiment the stimulator is configured to generate saidelectrical stimulation in accordance with at least one stimulationprogram, wherein said stimulation program includes at least one musclerecruitment program configured to generate an electrical stimulationdefined by the following stimulation parameters: a current intensitybetween 5 mA to 10 mA, preferably 6 mA to 10 mA; a frequency between 15Hz to 50 Hz, preferably 25 Hz to 45 Hz, more preferably 30 Hz to 40 Hz;and a pulse width between 50 μs to 300 μs, preferably 225 μs to 275 μs,more preferably 200 μs to 250 μs.

In an embodiment the stimulator is configured to generate saidelectrical stimulation in accordance with at least one stimulationprogram, wherein said stimulation program includes at least one musclerehabilitation program configured to generate an electrical stimulationdefined by the following stimulation parameters: a current intensitybetween 1 mA to 4 mA, preferably 2 mA to 4 mA; a frequency between 15 Hzto 50 Hz, preferably 20 Hz to 45 Hz, more preferably 30 Hz to 40 Hz;and, a pulse width between 50 μs to 300 μs, preferably 225 μs to 275 μs,more preferably 200 μs to 250 μs.

In an embodiment the stimulator is configured to generate saidelectrical stimulation in accordance with at least one stimulationprogram, wherein said stimulation program includes at least oneneuromuscular retraining program configured to generate an electricalstimulation defined by the following stimulation parameters: a currentintensity between 1 mA to 4 mA, between 2 mA to 4 mA; a frequencybetween 50 Hz to 150 Hz, preferably between 70 Hz to 130 Hz, even morepreferably 90 Hz to 110 Hz; and, a pulse width between 500 μs to 1000μs, preferably between 600 μs to 900 μs, more preferably 700 μs to 800μs.

In an embodiment the stimulator is configured to set the currentintensity according to an intensity determination programme, wherein thecurrent intensity is adjusted to a value between the stimulationperception threshold and stimulation discomfort threshold.

In an embodiment the stimulator is configured to selectively increasethe electrical stimulation intensity between at least two sleepingsessions; preferably increase the electrical stimulation by 1% to 25%.

In an embodiment the stimulator is configured to selectively increasethe electrical stimulation intensity between each and every consecutivesleeping session; preferably increase the electrical stimulation by 1%to 25%.

In an embodiment the stimulator is configured to apply a time-limitedelectrical pre-stimulation current between the left and/or rightelectrode and the subject skin to reduce the skin impedance.

In an embodiment the stimulator is configured to apply a time-limitedelectrical pre-stimulation current between the left and/or rightelectrode and the subject skin, current which has a pulse width of aboutor below 100 p and/or a pulse frequency of about or above 100 Hz.

In an embodiment the inter electrode distance between at least twoelectrically conductive elements of at least one electrode is between 15mm to 25 mm, preferably 16 mm to 24 mm, more preferably 17 mm to 23 mm,even more preferably 18 mm to 22 mm, even more preferably 19 mm to 21mm, even more preferably about 20 mm.

In an embodiment the diameter of at least one electrically conductiveelement of at least one electrode is between 10 mm to 20 mm, preferably11 mm to 19 mm, more preferably 12 mm to 18 mm, even more preferably 13mm to 17 mm, even more preferably 14 mm to 16 mm.

In an embodiment the wearable device comprises a sensing unit configuredfor recording of mandibular movement of the subject and a processingunit operatively connected to said sensing unit; wherein the processingunit is configured to receive, from said sensing unit, mandibularactivity data; and, determine, from the mandibular activity data, one ormore mandibular features. In an embodiment the mandibular featureincludes at least the position, rotation or displacement of themandible.

In an embodiment the wearable device comprises a sensing unit configuredfor recording of mandibular movement of the subject and a processingunit operatively connected to said sensing unit; wherein the processingunit is configured to receive, from said sensing unit, mandibularactivity data; and, determine, from the mandibular activity data, one ormore mandibular features, preferably including at least a position, arotation and/or a displacement of the subject's mandible and/or head.

In an embodiment the wearable device comprises a sensing unit thatcomprises at least one gyroscope and/or accelerometer configured forrecording mandibular movement; wherein the sensing unit is mounted onthe subject's mandible.

In an embodiment the wearable device comprises a sensing unit that ismounted on the left and/or right electrode; preferably on the leftand/or right masseter muscle; preferably on the left and/or rightelectrode mounted on the left and/or right masseter muscle.

In an embodiment the processing is configured to receive, from saidsensing unit, respiratory activity data; and, determine, from therespiratory activity data, one or more respiratory features. In anembodiment the respiratory feature includes at least a sleep disturbedbreathing marked with increased respiratory effort and/or a sleeprespiratory disturbance.

In an embodiment the processing unit is configured to determine from therespiratory activity data a stimulation response and compare saidstimulation response with a desired response, the desired responseconsisting of a decrease in the respiratory effort of a sleepingsubject; and to adjust at least one stimulation parameter if adifference between said stimulation response and said desired responseis determined to effectuate the desired response. In an embodiment thedesired response includes an adjusting of at least one stimulationparameter, preferably adjusting the current intensity.

In an embodiment the processing unit comprises a respiratory effortdetection module configured to detect an increase in respiratory effortin the subject's mandibular activity data, preferably from one or moremandibular features, and adjust one or more stimulation parametersand/or stimulation programs to reduce respiratory effort.

In an embodiment said respiratory effort detection module, upondetection of an increase in respiratory effort, is configured toincrease the current intensity by 10%, 20%, 30%, 40%, 50% or more,increase the stimulation period of the duty cycle by 10%, 20%, 30%, 40%,50% or more, and/or decrease the rest period of the duty cycle by 10%,20%, 30%, 40%, 50% or more.

In an embodiment said respiratory effort detection module, upondetection of a decrease in respiratory effort, is configured to decreasethe current intensity by 10%, 20%, 30%, 40%, 50% or more, decrease thestimulation period of the duty cycle by 10%, 20%, 30%, 40%, 50% or more,and/or increase the rest period of the duty cycle by 10%, 20%, 30%, 40%,50% or more.

In an embodiment the processing unit comprises a respiratory disturbancedetection module configured to detect the presence of a respiratorydisturbance in the subject's mandibular activity data, preferably fromone or more mandibular features, and adjust one or more stimulationparameters and/or stimulation programs to reduce, preferably prevent,the occurrence of a respiratory disturbance.

In an embodiment said respiratory disturbance detection module, upondetection of a respiratory disturbance, is configured to increase thecurrent intensity by 10%, 20%, 30%, 40%, 50% or more, increase thestimulation period of the duty cycle by 10%, 20%, 30%, 40%, 50% or more,and/or decrease the rest period of the duty cycle by 10%, 20%, 30%, 40%,50% or more.

In an embodiment the processing unit comprises a muscle fatiguedetection module configured to detect the presence of muscle fatigue inthe subject's mandibular activity data, preferably from the one or moremandibular features, and adjust one or more stimulation parametersand/or stimulation programs to reduce muscle fatigue.

In an embodiment said muscle fatigue detection module, upon detection ofmuscle fatigue, is configured to decrease the current intensity by 10%,20%, 30%, 40%, 50% or more, decrease the stimulation period of the dutycycle by 10%, 20%, 30%, 40%, 50% or more, and/or increase the restperiod of the duty cycle by 10%, 20%, 30%, 40%, 50% or more.

In an embodiment said muscle fatigue detection module, upon detection ofmuscle fatigue, is configured to terminate the recruitment programand/or initiate the rehabilitation program.

In an embodiment said muscle fatigue detection module is configured todetect the presence of peripheric muscular or fibre fatigue; and, upondetection of peripheric muscular or fibre fatigue, adjust one or morestimulation parameters by reducing the current intensity, preferably by10%, 20%, 30%, 40%, 50% or more; preferably by initiating a stimulationdefined by one or more stimulation parameter including a decreasedcurrent intensity of the electrical stimulation.

In an embodiment said muscle fatigue detection module is configured todetect the presence of spinal or supraspinal fatigue; and, upondetection of spinal or supraspinal fatigue, adjust one or morestimulation parameters by increasing the frequency, preferably by 10%,20%, 30%, 40%, 50% or more, and/or increasing the pulse width of theelectrical stimulation, preferably by 10%, 20%, 30%, 40%, 50% or more;preferably by initiating a stimulation defined by one or morestimulation parameter including an increased frequency and/or increasedpulse width of the electrical stimulation.

In an embodiment the processing unit is configured to receive, from saidsensing unit, sleeping activity data; and determine, from the sleepingactivity data, or more sleeping features. In an embodiment themandibular feature includes at least a sleeping state and/or a sleepingstage of the subject.

In an embodiment the processing unit is configured to determine, fromthe sleeping activity data, the sleeping state of the subject, whichsleeping state includes at least an awake state and/or an asleep state;and instruct the stimulator to initiate the electrical stimulationduring the asleep state and/or to terminate the electrical stimulationduring the awake state.

In an embodiment the processing unit is configured to determine, fromthe sleeping activity data, the sleeping stage of the subject, whichsleeping stage includes at least a light sleeping (N1) stage, a lightsleeping (N2) stage, a REM stage, and/or a deep sleeping (N3) stage; andinstruct the stimulator to initiate the electrical stimulation duringthe light sleeping (N1 and/or N2) stage and/or REM stage, and/or toterminate the electrical stimulation during the deep sleeping (N3)stage.

In an embodiment the processing unit comprises a sleeping stagedetermination module configured to determine a sleeping stage of thesubject including at least an awake state and asleep state, and adjustone or more stimulation parameters and/or stimulation programs when achange in sleeping stage is determined.

In an embodiment said sleeping stage determination module, upondetection of the awake stage, is configured to terminate the electricalstimulation and/or adjust one or more stimulation parameters and/orstimulation programs to reduce the stimulation efficiency; preferably byterminating the recruitment program and/or decreasing the currentintensity by 10%, 20%, 30%, 40%, 50% or more, decreasing the stimulationperiod of the duty cycle by 10%, 20%, 30%, 40%, 50% or more, and/orincreasing the rest period of the duty cycle by 10%, 20%, 30%, 40%, 50%or more.

In an embodiment said sleeping stage determination module, upondetection of the asleep stage, is configured to initiate the electricalstimulation and/or adjust one or more stimulation parameters and/orstimulation programs to increase the stimulation efficiency; preferablyby initiating the recruitment program and/or increasing the currentintensity by 10%, 20%, 30%, 40%, 50% or more, increasing the stimulationperiod of the duty cycle by 10%, 20%, 30%, 40%, 50% or more, and/ordecreasing the rest period of the duty cycle by 10%, 20%, 30%, 40%, 50%or more.

In an embodiment said sleeping stage determination module is furtherconfigured to determine a light sleeping (N1 and/or N2) stage and/or REMstage; and, wherein, upon detection of the light sleeping (N1 and/or N2)stage and/or REM stage, said sleeping stage determination module isconfigured to initiate the electrical stimulation and/or adjust one ormore stimulation parameters to increase the stimulation efficiency;preferably by increasing the current intensity by 10%, 20%, 30%, 40%,50% or more, increasing the stimulation period of the duty cycle by 10%,20%, 30%, 40%, 50% or more, and/or decreasing the rest period of theduty cycle by 10%, 20%, 30%, 40%, 50% or more.

In an embodiment said sleeping stage determination module is furtherconfigured to determine a light sleeping (N1 and/or N2) stage and/or REMstage; and, wherein, upon detection of the light sleeping (N1 and/or N2)stage and/or REM stage, said sleeping stage determination module isconfigured to initiate the recruitment program and/or terminate theretraining program.

In an embodiment said sleeping stage determination module is furtherconfigured to determine a deep sleeping (N3) stage; and, wherein, upondetection of the deep sleeping (N3) stage, said sleeping stagedetermination module is configured to adjust one or more stimulationparameters to decrease the stimulation efficiency; preferably bydecreasing the current intensity by 10%, 20%, 30%, 40%, 50% or more,decreasing the stimulation period of the duty cycle by 10%, 20%, 30%,40%, 50% or more, and/or increasing the rest period of the duty cycle by10%, 20%, 30%, 40%, 50% or more.

In an embodiment said sleeping stage determination module is furtherconfigured to determine a deep sleeping (N3) stage; and, wherein, upondetection of the deep sleeping (N3) stage, said sleeping stagedetermination module is configured to terminate the recruitment programand/or initiate the retraining program.

In an embodiment the processing unit is configured to determine thesleeping state and/or stage by

-   -   dividing the mandibular activity data into epochs of a specific        time; and,    -   applying a mathematical model to assign a sleeping state and/or        sleeping stage to every epoch; wherein said mathematical model        comprises the step of    -   extracting at least one feature from the recorded mandibular        movement data for every epoch;    -   tracking the value of said extracted feature across every epoch;    -   setting a feature specific threshold value; and,    -   adjusting the sleeping state and/or sleeping stage of an epoch        if the extracted feature value exceeds the feature specific        threshold value.

In an embodiment the sensing unit comprises at least one gyroscopeconfigured for recording mandibular movement of the subject's mandible.

In an embodiment the sensing unit comprises at least one gyroscope, atleast one accelerometer and optionally also at least one magnetometer.

In an embodiment the sensing unit is provided on the left and/or rightelectrode.

In an embodiment the wearable device comprises a collar for housing thestimulator; wherein the collar is adapted for placement around thesubject's neck and/or onto the subject's shoulders.

In an embodiment the left and/or right electrode is connected to thecollar with a connective cable, the length of which may be adjusted.

An aspect of the present disclosure relates to a method for mounting ofan electrode on a selected portion of the subject's skin correspondingwith the position of a masseter muscle, the method comprising the stepsof:

-   -   (i) identifying the gonial angle (Go), preferably the corner        angle of the mandible;    -   (ii) identifying the zygomatic arch (Za), preferably the outer        corner of the eye;    -   (iii) identifying the masseter muscle extending from said gonial        angle (Go) towards said zygomatic arch (Za);    -   (iv) identifying a target stimulation zone (S) on said masseter        muscle, preferably ranging from the gonial angle (Go) up to        about halfway the distance between the gonial angle (Go) and the        zygomatic arch (Za) along the direction of the masseter muscle        fibre; and,    -   (v) mounting the electrode on said target stimulation zone (S).

In an embodiment of the method for mounting the electrode is a bipolarelectrode comprising two conductive surfaces, wherein the firstelectrically conductive element is mounted on the masseter muscle'smotor point, preferably adjacent to the gonial angle (Go), and thesecond electrically conductive element is mounted along the direction ofthe masseter muscle fibre, preferably about halfway the distance betweenthe gonial angle (Go) and the zygomatic arch (Za) along the direction ofthe masseter muscle fibre.

An aspect of the present disclosure relates to a method for decreasingthe respiratory effort of a subject during said subject's sleep, themethod comprising:

-   -   selecting a portion of the subject's skin corresponding with the        position of at least one left target muscle including a left        masseter, a left pterygoid and/or a left temporalis muscle, and        mounting at least one left bipolar electrode comprising at least        two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the left target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the left target muscle fibre;    -   selecting a portion of the subject's skin corresponding with the        position of at least one right target muscle including a right        masseter, a right pterygoid and/or a right temporalis muscle,        and mounting at least one left bipolar electrode comprising at        least two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the right target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the right target muscle fibre;    -   applying a biphasic transcutaneous electrical stimulation        between the two electrically conductive elements of the left and        right bipolar electrodes, which electrical stimulation promotes        the contraction of the target muscles to controllably elevate        the subject's mandible so that the respiratory effort can be        decreased; wherein said electrical stimulation is generated        according to a duty cycle that has a stimulation period of 1 sec        to 20 sec and/or a rest period of 1 sec to 20 sec.

An aspect of the present disclosure relates to a method for recruitingof a target muscle to decrease the respiratory effort of a subjectduring said subject's sleep, the method comprising:

-   -   selecting a portion of the subject's skin corresponding with the        position of at least one left target muscle including a left        masseter, a left pterygoid and/or a left temporalis muscle, and        mounting at least one left bipolar electrode comprising at least        two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the left target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the left target muscle fibre;    -   selecting a portion of the subject's skin corresponding with the        position of at least one right target muscle including a right        masseter, a right pterygoid and/or a right temporalis muscle,        and mounting at least one left bipolar electrode comprising at        least two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the right target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the right target muscle fibre;    -   applying a biphasic transcutaneous electrical stimulation        between the two electrically conductive elements of the left and        right bipolar electrodes, which electrical stimulation promotes        the contraction of the target muscles to controllably elevate        the subject's mandible so that the respiratory effort can be        decreased;    -   wherein said electrical stimulation is generated according to        the following stimulation parameters: a current intensity        between 5 mA to 10 mA, preferably 6 mA to 10 mA; a frequency        between 15 Hz to 50 Hz, preferably 25 Hz to 45 Hz, more        preferably 30 Hz to 40 Hz; a pulse width between 50 μs to 300        μs, preferably 225 μs to 275 μs, more preferably 200 μs to 250        μs; and, a duty cycle with a stimulation period of 1 sec to 20        sec and/or a rest period of 1 sec to 20 sec.

An aspect of the present disclosure relates to a method forrehabilitating the muscle function of a target muscle to decrease therespiratory effort of a subject during said subject's sleep, the methodcomprising:

-   -   selecting a portion of the subject's skin corresponding with the        position of at least one left target muscle including a left        masseter, a left pterygoid and/or a left temporalis muscle, and        mounting at least one left bipolar electrode comprising at least        two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the left target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the left target muscle fibre;    -   selecting a portion of the subject's skin corresponding with the        position of at least one right target muscle including a right        masseter, a right pterygoid and/or a right temporalis muscle,        and mounting at least one left bipolar electrode comprising at        least two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the right target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the right target muscle fibre;    -   applying a biphasic transcutaneous electrical stimulation        between the two electrically conductive elements of the left and        right bipolar electrodes, which electrical stimulation promotes        the contraction of the target muscles to controllably elevate        the subject's mandible so that the respiratory effort can be        decreased;    -   wherein said electrical stimulation is generated according to        the following stimulation parameters: a current intensity        between 1 mA to 4 mA, preferably 2 mA to 4 mA; a frequency        between 15 Hz to 50 Hz, preferably 20 Hz to 45 Hz, more        preferably 30 Hz to 40 Hz; a pulse width between 50 μs to 300        μs, preferably 225 μs to 275 μs, more preferably 200 μs to 250        μs; and, a duty cycle with a stimulation period of 1 sec to 20        sec and/or a rest period of 1 sec to 20 sec.

An aspect of the present disclosure relates to a method for retrainingof a neuromuscular related circuit to decrease the respiratory effort ofa subject during said subject's sleep, the method comprising:

-   -   selecting a portion of the subject's skin corresponding with the        position of at least one left target muscle including a left        masseter, a left pterygoid and/or a left temporalis muscle, and        mounting at least one left bipolar electrode comprising at least        two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the left target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the left target muscle fibre;    -   selecting a portion of the subject's skin corresponding with the        position of at least one right target muscle including a right        masseter, a right pterygoid and/or a right temporalis muscle,        and mounting at least one left bipolar electrode comprising at        least two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the right target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the right target muscle fibre;    -   applying a biphasic transcutaneous electrical stimulation        between the two electrically conductive elements of the left and        right bipolar electrodes, which electrical stimulation promotes        the contraction of the target muscles to controllably elevate        the subject's mandible so that the respiratory effort can be        decreased; wherein said electrical stimulation is generated        according to the following stimulation parameters: a current        intensity between 1 mA to 4 mA, between 2 mA to 4 mA; a        frequency between 50 Hz to 150 Hz, preferably between 70 Hz to        130 Hz, even more preferably 90 Hz to 110 Hz; a pulse width        between 500 μs to 1000 μs, preferably between 600 μs to 900 μs,        more preferably 700 μs to 800 μs; and, a duty cycle with a        stimulation period of 1 sec to 20 sec and/or a rest period of 1        sec to 20 sec.

DESCRIPTION OF THE FIGURES

The following description of the figures of specific embodiments of thedisclosure are merely exemplary in nature and is not intended to limitthe present teachings, their application or uses.

Throughout the drawings, the corresponding reference numerals indicatethe following parts and features: stimulation region (5); superficialmasseter (SM); medial pterygoid (MP); anterior temporalis (AT); gonialangle (Go); zygomatic arch (Za); wearable device (10); electrode (100);electrically conductive element (110); connective cable (150); wearablegarment (200), e.g., collar or headband.

FIG. 1 is an illustration of the stimulation region (S) on a subject'sskin for positioning of an electrode (100) according to a preferredembodiment of the present invention.

FIG. 2 is a schematic drawing of the wearable device (10) configured forstimulation of masseter muscles according to a preferred embodiment ofthe present invention.

FIG. 3 is a perspective view of the wearable device (10) configured forstimulation of masseter muscles according to another preferredembodiment of the present invention.

FIG. 4 is a perspective view of the wearable device (10) configured forstimulation of masseter muscles according to another preferredembodiment of the present invention.

FIG. 5 is a perspective view of the wearable device (10) configured forstimulation of masseter and/or temporalis muscles according to anotherpreferred embodiment of the present invention.

FIG. 6 is a perspective view of the wearable device (10) configured forstimulation of pterygoid muscles according to another preferredembodiment of the present invention.

FIG. 7 is a lateral view of a skull with reference landmarks and linesfor identifying the stimulation region (S) according to anotherpreferred embodiment of the present invention.

FIG. 8 is a lateral view of a head with reference landmarks and linesfor identifying the stimulation region (S) according to anotherpreferred embodiment of the present invention.

FIG. 9 is a placement guide illustrating a method for placement of theelectrode (100) on the stimulation region (S) according to anotherpreferred embodiment of the present invention.

FIG. 10 is an illustration of a bipolar electrode (100) according to apreferred embodiment of the present invention.

FIG. 11 is a schematic of the working principle of the wearable device(10) according to a preferred embodiment of the present invention.

FIG. 12 shows the mandibular movement (MM data) recorded by a chinsensor for the sleeping stage study discussed in Example 6.

FIG. 13 shows the mandibular movement (MM data) recorded by a cheeksensor for the sleeping stage study discussed in Example 6.

FIG. 14 shows the frequency distribution of standard deviation (SD)values for both sleep (light) and wake (dark) states as discussed inExample 6.

FIG. 15 shows the sensitivity/specificity across all possible SD valuesfor detection of sleep and wake state for the sleeping stage study asdiscussed in Example 6.

FIG. 16 shows the frequency distribution of maximum (MAX) values forboth sleep (light) and wake (dark) states as discussed in Example 6.

FIG. 17 shows the sensitivity/specificity across all possible MAX valuesfor detection of sleep and wake state as discussed in Example 6.

FIG. 18 shows the cut-off configuration parameters for the fixed cut-offmodel as discussed in Example 6.

FIG. 19 shows a table with the data analysis algorithm configured forwake state detection of the fixed cut-off model as discussed in Example6.

FIG. 20 shows a table with the data analysis algorithm configured forbalanced wake/sleeping state detection of the fixed cut-off model asdiscussed in Example 6.

FIG. 21 shows a table with the data analysis algorithm configured forsleeping state detection of the fixed cut-off model as discussed inExample 6.

FIG. 22 shows the cut-off configuration parameters for the personalisedcut-off model as discussed in Example 6.

FIG. 23 shows a table with the data analysis algorithm configured forwake state detection of the personalised cut-off model as discussed inExample 6.

FIG. 24 shows a table with the data analysis algorithm configured forbalanced wake/sleeping state detection of the personalised cut-off modelas discussed in Example 6.

FIG. 25 shows a table with the data analysis algorithm configured forsleeping state detection of the personalised cut-off model as discussedin Example 6.

FIG. 26 shows a Bland-Altman graph of the comparison of chin sensor datawith the algorithm data analysis of the cheek sensor data.

FIG. 27 shows a Bland-Altman graph of the comparison of the chin sensordata with the sleep/wake detection rule based on standard deviations(SD) of the cheek sensor data.

FIG. 28 shows a Bland-Altman graph of the comparison of the chin sensordata with the sleep/wake detection rule based on maximum values (MAX) ofthe cheek sensor data.

DETAILED DESCRIPTION

The present disclosure will be described with respect to particularembodiments, but the disclosure is not limited thereto but only by theclaims. Any reference signs in the claims shall not be construed aslimiting the scope thereof.

As used herein, the singular forms “a”, “an”, and “the” include bothsingular and plural referents unless the context clearly dictatesotherwise.

The terms “comprising”, “comprises” and “comprised of” as used hereinare synonymous with “including”, “includes” or “containing”, “contains”,and are inclusive or open-ended and do not exclude additional,non-recited members, elements or method steps. The terms “comprising”,“comprises” and “comprised of” when referring to recited members,elements or method steps also include embodiments which “consist of”said recited members, elements or method steps.

The recitation of numerical ranges by endpoints includes all numbers andfractions subsumed within the respective ranges, as well as the recitedendpoints.

Furthermore, the terms first, second, third and the like in thedescription and in the claims, are used for distinguishing betweensimilar elements and not necessarily for describing a sequential orchronological order, unless specified. It is to be understood that theterms so used are interchangeable under appropriate circumstances andthat the embodiments of the disclosure described herein are capable ofoperation in other sequences than described or illustrated herein.

Unless otherwise defined, all terms used in disclosing the invention,including technical and scientific terms, have the meaning as commonlyunderstood by one of ordinary skill in the art to which this disclosurebelongs. By means of further guidance, definitions for the terms used inthe description are included to better appreciate the teaching of thepresent invention. The terms or definitions used herein are providedsolely to aid in the understanding of the invention.

Reference throughout this specification to “one embodiment” or “anembodiment” means that a particular feature, structure or characteristicdescribed in connection with the embodiment is included in at least oneembodiment of the present invention. Thus, appearances of the phrases“in one embodiment” or “in an embodiment” in various places throughoutthis specification are not necessarily all referring to the sameembodiment. Furthermore, the particular features, structures orcharacteristics may be combined in any suitable manner, as would beapparent to a person skilled in the art from this disclosure, in one ormore embodiments. Furthermore, while some embodiments described hereininclude some, but not other features included in other embodiments,combinations of features of different embodiments are meant to be withinthe scope of the invention, and form different embodiments, as would beunderstood by those in the art. For example, in the following claims anddescription, any of the claimed or described embodiments can be used inany combination.

The terms “left”, “right”, “front”, “back”, “top”, “bottom”, “over”,“under”, and the like in the description and in the claims, if any, areused for descriptive purposes and not necessarily for describingpermanent relative positions. It is to be understood that the terms soused are interchangeable under appropriate circumstances such that theembodiments described herein are, for example, capable of operation inother orientations than those illustrated or otherwise described herein.The term “coupled”, as used herein, is defined as directly or indirectlyconnected in an electrical or nonelectrical (i.e. physical) manner.Objects described herein as being “adjacent to” each other may be inphysical contact with each other, in close proximity to each other, orin the same general region or area as each other, as appropriate for thecontext in which the phrase is used. Occurrences of the phrase “in oneembodiment”, or “in one aspect”, herein do not necessarily all refer tothe same embodiment or aspect.

As used herein, the term “substantially” refers to the complete ornearly complete extent or degree of an action, characteristic, property,state, structure, item, or result. For example, an object that is“substantially” enclosed would mean that the object is either completelyenclosed or nearly completely enclosed. The exact allowable degree ofdeviation from absolute completeness may in some cases depend on thespecific context. However, generally speaking the nearness of completionwill be so as to have the same overall result as if absolute and totalcompletion were obtained. The use of “substantially” is equallyapplicable when used in a negative connotation to refer to the completeor near complete lack of an action, characteristic, property, state,structure, item, or result. For example, a composition that is“substantially free of” particles would either completely lackparticles, or so nearly completely lack particles that the effect wouldbe the same as if it completely lacked particles. In other words, acomposition that is “substantially free of” an ingredient or element maystill actually contain such item as long as there is no measurableeffect thereof.

As used herein, the term “about” is used to provide flexibility to anumerical range endpoint by providing that a given value may be “alittle above” or “a little below” the endpoint. Unless otherwise stated,use of the term “about” in accordance with a specific number ornumerical range should also be understood to provide support for suchnumerical terms or range without the term “about”. For example, for thesake of convenience and brevity, a numerical range of “about 50angstroms to about 80 angstroms” should also be understood to providesupport for the range of “50 angstroms to 80 angstroms.” Furthermore, itis to be understood that in this specification support for actualnumerical values is provided even when the term “about” is usedtherewith. For example, the recitation of “about” 30 should be construedas not only providing support for values a little above and a littlebelow 30, but also for the actual numerical value of 30 as well.

Reference in this specification may be made to devices, structures,systems, or methods that provide “improved” performance. It is to beunderstood that unless otherwise stated, such “improvement” is a measureof a benefit obtained based on a comparison to devices, structures,systems or methods in the prior art. Furthermore, it is to be understoodthat the degree of improved performance may vary between disclosedembodiments and that no equality or consistency in the amount, degree,or realization of improved performance is to be assumed as universallyapplicable.

In addition, it should be understood that embodiments of the presentdisclosure may include hardware, software, and electronic components ormodules that, for purposes of discussion, may be illustrated anddescribed as if the majority of the components were implemented solelyin hardware. However, one of ordinary skill in the art, and based on areading of this detailed description, would recognize that, in at leastone embodiment, the electronic based aspects of the present disclosuremay be implemented in software (e.g., instructions stored onnon-transitory computer-readable medium) executable by one or moreprocessing units, such as a microprocessor and/or application specificintegrated circuits (“ASICs”). As such, it should be noted that aplurality of hardware and software-based devices, as well as a pluralityof different structural components may be utilized to implement theinvention. For example, “servers” and “computing devices” described inthe specification can include one or more processing units, one or morecomputer-readable medium modules, one or more input/output interfaces,and various connections (e.g., a system bus) connecting the components.

As described above, there is a need to remedy the issues and limitationsof state of art treatments for sleep disturbed breathing marked withrespiratory effort (SDB). The present disclosure relates to means andmethods for decreasing the respiratory effort of a sleeping subjectand/or prevent the occurrence of sleep respiratory disturbances. Inparticular, the present disclosure aims to provide transcutaneouselectrical stimulation to muscles controlling the movement of themandible of a subject to adjust their contribution to the sleeprespiratory activity and reduce the subject's respiratory effort duringor after sleep.

The electrical stimulation to the muscles may be applied during asession with a time limit, which will be referred to as the stimulationsession throughout the present disclosure. The stimulation sessionaccording to the present disclosure may be configured for effectuating atherapeutic effect, for instance to reduce the occurrence of sleeprespiratory disorders or sleep-disordered breathing, or it may beconfigured for non-therapeutic purposes, such as a reduction of snoringor sleep related noises, or improving the sleeping quality. The timelimit of the session may be predetermined or variable.

Accordingly, the present disclosure relates to wearable devices forproviding a transcutaneous electrical stimulation to muscles controllingthe movement of the mandible of a subject to decrease the respiratoryeffort of said subject during sleep and/or prevent the occurrence ofsleep respiratory disturbances.

Further, the present disclosure aims to provide for a retraining of thesubject's brain through the provided electrical stimulation to decreasethe central respiratory drive of the stimulated muscles.

Further, the disclosure also relates to wearable devices to monitor astimulation response of a sleeping subject, preferably in response to atranscutaneous electrical stimulation provided by the herein disclosedwearable devices for providing a transcutaneous electrical stimulation.The wearable device may be configured to determine the stimulationresponse directly through a physiological response of the sleepingsubject to the electrical stimulation, or indirectly through an effecteffectuated by the electrical stimulation, such as a reduction of thesubject's respiratory effort and/or occurrence of sleep respiratorydisturbances.

Further, the disclosure also relates to wearable devices to monitor arespiratory activity of a sleeping subject. The wearable device may beconfigured to determine sleep disturbed breathing marked with increasedrespiratory effort and/or the occurrence of a sleep respiratorydisturbance. The wearable devices to monitor a respiratory activity of asleeping subject may be linked or combined with the wearable devices forproviding a transcutaneous electrical stimulation as described herein.

Further, the disclosure also relates to wearable devices to monitor asleeping activity of a sleeping subject. The wearable device may beconfigured to determine a sleep state of a subject, which may include anawake state and an asleep state, and/or a sleep stage of a sleepingsubject, which may include a light sleeping (N1) stage, a light sleeping(N2) stage, a REM stage, and/or a deep sleeping (N3) stage. The wearabledevices to monitor a sleeping activity of a sleeping subject may be usedto adjust the transcutaneous electrical stimulation The wearable devicesto monitor a sleeping activity of a sleeping subject may be linked orcombined with the wearable devices for providing a transcutaneouselectrical stimulation as described herein.

Selective electrical stimulation of muscles controlling the movement ofthe mandible may allow for the mandible to be controllably moved into anelevated and anterior position and subsequently stabilized in saidelevated and anterior position during subject sleep. The mandible can beused as a lever to stiffen the whole pharyngeal musculature whichanchors to the mandibular arch and controls the opening of the upperairways. By finely adjusting the position of the mandible, therelationship between the muscular fibre tension and its length can becontrolled, as well the relationship between the fibre force and itsvelocity. The genioglossus muscle anchors itself to the elevatedposition of the mandible and may thus further contribute to the openingof the upper airways. Also, the attached muscles may elevate the hyoidbone to a more advanced and upper position. The functional result is adilation of the pharynx to substantially open the upper airways andinstruct the brain to decrease the necessary level of respiratoryeffort.

Muscles for controlling the movement of the mandible may include theelevator muscles (i.e., muscles which contraction raises the position ofthe mandible), which includes the masseter, temporalis, medial pterygoidand superior belly of the lateral pterygoid, and/or the depressormuscles (i.e., muscles which contraction lowers the position of themandible), which includes the anterior digastric, geniohyoid, mylohyoidand inferior belly of the lateral pterygoid. It is understood that anyreferences to electrical stimulation of “muscles” as used herein refersto a stimulation of the listed elevator and/or depressor muscles. Anembodiment of the present disclosure may provide for a stimulation of asingle muscle type, for example only the masseter muscle, only thepterygoid muscle or only the temporalis muscle. An example of massetermuscle only stimulation is shown in FIG. 2 , and an example of pterygoidmuscle only stimulation is shown in FIG. 6 . Another embodiment of thepresent disclosure may provide for a dual stimulation of a two differentmuscle types, for example the masseter and the temporalis muscles, themasseter and the pterygoid muscles, the temporalis and the pterygoidmuscles, or the masseter and temporalis and pterygoid muscles, eithersequentially or simultaneously, to effectuate the mandibular elevationand stabilisation. An example of dual masseter and temporalis musclestimulation is shown in FIG. 5 . Another embodiment of the presentdisclosure may provide for a triple stimulation of a three differentmuscle types, for example the masseter, temporalis and pterygoidmuscles, either sequentially or simultaneously, to effectuate themandibular elevation and stabilisation.

The electrical stimulation on the muscles for controlling the movementof the mandible may also provide for secondary effects on the othermuscles connecting to the mandible. For instance, the genioglossus isanchored to the mental spines (on the internal face of the median lineof the gnathion, the bony point on which the genioglossus hangs) at theinner side of the gnathion—by consequence when moving the mandibleduring elevation, the stimulation according to the present disclosurechanges the spatial position of the anterior attachment point of thegenioglossus. This may change the resting length of the genioglossusfibres by traction, a condition well known to induce a contraction ofthe anchored fibres (myotatic reflex). The risk of dry tongue is minimalwhen mouth is closed. Choking and gasping are avoided because the tongueis kept at an anterior location in the oral cavity.

Further, about the oral floor musculature (mylohyoid-geniohyoid-anteriorbelly of the digastric): when elevated, the mandible develops a leverageaction on the oral floor muscles and these muscles become able tocontract and to stiffen the upper airways while the hyoid bone positionis regulated by other posterior and inferior muscles. Basically, themandible is a mobile bone with several upper airway muscle attachmentsoriginating from surrounding locations. The mandible moves in responseto active muscle contraction. This movement results in transfer ofapplied loads originating from one direction to other regions throughoutthe upper airway. The masseter displaces the mandible to an upper andforward position, and this enables also the other mobile hyoid bone toimprove upper airway patency. These muscles attached directly orindirectly to the mandible are in a complex and intricate relationshipwith the final objective during sleep to ensure the local airflowcirculation while diaphragm is going to constrict and create in theupper airway a sub atmospheric pressure.

It has been discovered that stimulation of the masseter, pterygoidand/or temporalis muscles are particularly effective for controlling andstabilising the elevation of the mandible and hence form a preferredembodiment of the present disclosure, specifically stimulation of thesuperficial masseter (sm), the medial pterygoid (mp) and the anteriortemporalis (at). To elaborate, the masseter, pterygoid and/or temporalismuscles are specifically dedicated to the elevation of the mandible andtherefore the mouth closing. These muscles are highly specialized andtrained to perform this task. They are performant in endurance and inresistance due to their particular fibre muscular isoforms that are notpresent in the other groups of muscles in the human body. They are alsoinvolved in other important living functions: mastication, swallowingand speaking. When the masseter and/or the temporalis are stimulated,neurons develop in its representation area on the motor cortex as withthe tongue—motor learning (neuroplasticity induced in corticomotorcontrol of jaw muscles—cortical neuroplasticity is the ability of thebrain to enhance a special skill with practice and to adapt orcompensate for changes in sensory input).

Additionally, focusing the stimulation on the masseter, pterygoid and/ortemporalis muscles only may reduce the discomfort experienced by thesubject and decrease the build-up of muscle fatigue. These effects mayfor example be observed in stimulation focusing on too many differentmuscles at the same time and/or focusing on muscles that are consideringas discomforting and/or easily fatigable, such the tongue. Accordingly,exclusive stimulation of the masseter, pterygoid and/or temporalismuscles form another preferred embodiment of the present disclosure.

There are different methods for effectuating electrical stimulation ofthe muscles, each method provoking a unique physiological response thatmay result in different technical effects and advantages. At least threedifferent methods for effectuating electrical stimulation arecontemplated in the present disclosure, specifically, recruiting themuscular fibres, rehabilitating the muscle function, and retraining theneuromuscular related circuit (through stimulation of the muscles).

To elaborate, recruiting the muscular fibres refers to a direct andacute muscle response to the electrical stimulation with directlymeasurable effects. Recruitment may hence be considered as a “basic”program for controlling the movement of the mandible during astimulation session, but will typically not provide a persisting effectafter the stimulation session has finished (i.e., when the stimulator isturned off).

Rehabilitating of the muscle function refers a training of the musclesthrough electrical stimulation that may improve the beneficial effectsof the stimulation across successive stimulation sessions.

Rehabilitation may hence be considered as an “advanced” program that mayprovide for a delayed and advantageously persisting effect, but mayrequire more than one, such as a plurality of successive stimulationsessions to achieve said effect.

Retraining of the neuromuscular related circuit refers to a centraleffect of the electrical stimulation on the central drive (directed onthe central neural circuits involved in the breathing activity of themotor branch of the trigeminal nerve from the subject's brain) that isprimarily aimed at achieving a persisting response after the stimulationsession is finished or discontinued. Retraining may hence be consideredas an “advanced” program that may provide for a persisting effect afterthe stimulation session has finished (i.e., when the stimulator isturned off), but may require more than one, such as a plurality ofsuccessive stimulation sessions to achieve said effect.

It may be appreciated that this initial overview of the stimulationmethods is only intended to aid readers in understanding the differencebetween the methods more quickly. Specific embodiments for each method,for example in the form of programs to be executed by the hereindisclosed stimulator, will be discussed throughout the presentdisclosure.

During general stimulation, the present disclosure may provide for aregulatory process of the central respiratory drive to reduce activeeffort needed for respiration and consequently relieve the sleepingsubject from a harmful sympathetic stress provoked by respiratorydisturbances. Further, the present disclosure may provide for aretraining process for the central respiratory drive to decrease thenatural drive of the muscles and restore respiratory ventilation, whichbenefits may persist after stimulation. These processes may also providefor improvement in airflow, SpO₂, noise, orofacial dyskinesias, etc.Accordingly, the present disclosure can be applied for treatment ofvarious disorders related to sleep disturbed breathing marked withrespiratory effort (SDB), such as airway obstruction or collapse.Additionally, the device may aid in alleviating the occurrence and/orintensity of snoring.

Mandibular elevation effectuated by the present disclosure may open theupper airways or upper respiratory tract by increasing the upper airwaywidth and/or reducing its collapsibility. The degree of mandibularelevation may be expressed as a % of maximum protrusive capacity or/andin millimetres (mm). Percentage of maximum protrusive capacity may belinked to potential side effects and percentage or millimetres toeffectiveness in opening the upper airway. Exemplary protrusionpositions may include 10% to 90% of the maximum mandibular protrusion.

It has been observed that recruiting and retraining of the muscles forcontrolling the movement of the mandible with “mild” transcutaneouselectrical stimulation does not achieve adequate results. However, thepresent disclosure presents evidence that a sufficiently strong closingof the mandible for a sufficiently long period of time may provideimproved short-term and/or long-term results. These results may betherapeutic in nature, for example by reducing the occurrence of sleeprespiratory disorders or sleep-disordered breathing, or they may benon-therapeutic, for example by reducing the amount of sleep relatednoises or improving the sleeping quality. Advantageously, the short-termand/or long-term may be combined to achieve an efficient stimulationresponse by first recruiting the stimulated muscles and furtherretraining these stimulated muscles to improve the stimulation responseand/or achieving persisting effects after termination of thestimulation. This way a synergistic effect can be achieved that goesbeyond the benefits of local stimulation methods of the art.

Within the context of an electrical stimulation, “sufficiently strongclosing” relates to the current intensity as experienced by the user atthe beginning of the stimulation while in a quiet position just beforefalling asleep, as a spontaneous (not voluntary) tendency of mouthclosure. The strength of the closing can be measured clinically by meansof a force meter (min contractive force (F), min % of muscular fibres)or by mandible movement (change in amplitude, mandible position). Withinthe context of an electrical stimulation, “sufficiently long closing”relates to the time that the mandible is kept in a high and forwardposition that may ensure the air circulation. For example, the mandiblecan be elevated to close the mouth during the stimulation period of theduty cycle and then the mandibular jaw keeping elevated during the restperiod of the duty cycle. The length of the closing can be measuredclinically by means of an airflow meter (airflow amplitude (%)) or bymandible movement (time and frequency, mandible position). Measurementof the efficacy of the stimulation may be found discussed in Example 3.

An initial overview of various aspects of the disclosure is providedbelow and specific embodiments are then described in further detail.This initial overview is intended to aid readers in understanding thetechnological concepts more quickly, but is not intended to identify keyor essential features thereof, nor is it intended to limit the scope ofthe claimed subject matter. The skilled person understands that thevarious aspects can be combined unless otherwise stated. As such, anyspecific embodiment of a specific aspect may be understood to constitutea specific embodiment of another aspect without the explicitlydiscussion thereof. For example, an embodiment of the device asdescribed below also forms an embodiment for the manufacturing of saiddevice, the use of said device, and so on.

An aspect of the present disclosure relates to a wearable device fordecreasing the respiratory effort of a subject during sleep, the devicecomprising:

-   -   at least one left electrode adapted to be positioned into        electrical contact with a selected portion of the subject's skin        ranging from a left muscle motor point to a left posterior angle        of the mandible;    -   at least one right electrode adapted to be positioned into        electrical contact with a selected portion of the subject's skin        ranging from a right muscle motor point to a right posterior        angle of the mandible;    -   a stimulator configured to apply a transcutaneous electrical        stimulation from the left electrode to at least one left muscle        and from the right electrode to at least one right muscle;        wherein the applied electrical stimulation promotes the        contraction of said left and right stimulated muscles to        controllably elevate the subject's mandible such that the upper        airway is opened.

In an embodiment at least one left electrode may be adapted to bepositioned into electrical contact with a selected portion of thesubject's skin ranging from a left masseter, pterygoid and/or temporalismuscle motor point to a left posterior angle of the mandible and thestimulator is configured to apply a transcutaneous electricalstimulation from the left electrode to the at least one left masseter,pterygoid and/or temporalis muscle.

In an embodiment the at least one right electrode may be adapted to bepositioned into electrical contact with a selected portion of thesubject's skin ranging from a right masseter, pterygoid and/ortemporalis muscle motor point to a right posterior angle of the mandibleand the stimulator is configured to apply a transcutaneous electricalstimulation from the right electrode to the at least one right masseter,pterygoid and/or temporalis muscle.

The electrodes, preferably the left and right electrodes may deliver theelectrical stimulation generated by the stimulator to the targetmuscles. According to an embodiment two or more electrodes may beprovided, at least one for each side of the mandible, specifically theleft and right electrode, such that the target muscles can bebilaterally stimulated.

In an embodiment the electrode may have an electrically conductiveelement with a diameter between 10 mm to 20 mm, preferably 11 mm to 19mm, more preferably 12 mm to 18 mm, even more preferably 13 mm to 17 mm,even more preferably 14 mm to 16 mm, for example about 15 mm. Typicallya circular electrically conductive element may be used, i.e., aconductive element with a circular surface area, but other geometricalshapes may also be contemplated, for example an oval element, squareelement, triangular element, etc. This may allow for covering the mostprominent muscles bulk to achieve an efficient stimulation response. Inanother embodiment a diameter of 10 mm or lower can be used and stillallow covering of the most prominent muscles bulk for targetedstimulation of smaller or more narrow muscles, such as the surface ofthe temporalis muscle.

In an embodiment the electrode may be a bipolar electrode, i.e., whereineach electrode comprises two electrically conductive elements that areapplied between the target stimulation zone and the tendon. An exampleof a bipolar electrode with two adjacently disposed electricallyconductive elements is shown in FIG. 10 . The distance between theadjacent electrically conductive elements of the bipolar electrode isdefined as the inter electrode distance. The inter electrode distancehas an important impact on the comfort of the stimulation. If thecomfort is improved, it may be possible for the patient to reach highercurrent intensities and thus improve the effectiveness of the treatment.In an embodiment the inter electrode distance may be between 10 mm to 30mm, preferably 15 mm to 25 mm, preferably 16 mm to 24 mm, morepreferably 17 mm to 23 mm, even more preferably 18 mm to 22 mm, evenmore preferably 19 mm to 21 mm, even more preferably about 20 mm.Typically a smaller inter electrode distance, for example 10 mm to 15mm, may be selected for stimulation of smaller muscles and a largerinter electrode distance, for example 20 mm to 30 mm, may be selectedfor stimulation of larger muscles, such as the temporalis.Advantageously, the adjacent surface electrodes may be aligned with themuscle fibre direction to stimulate the same motor unit response twicebut spatially shifted along the muscle.

In an embodiment the electrode can be repeatedly attached to the skin.Repeated attachment is advantageous for the device to be reusable oversuccessive sleeping sessions. The electrodes are conveniently attachedto stay in place during normal head and body movements. The electrodesmay be provided with adhesive surfaces, which allow for easy attachmentto the skin. Each electrode may be provided with a surface which isadapted for skin-dismountable attachment. Advantageously, each electrodemay be configured to ensure electric conductivity such that comfort andeffectiveness can be improved.

In an embodiment the electrode surface may be provided with an adhesivehydrogel to ensure a low resistive contact between the electrode and theskin. The electrode surface may be replaceable when the adhesive layeris worn out with repeated use, or alternatively, the adhesive layer maybe replenished. In an alternative embodiment single use electrodes canbe contemplated. In another embodiment electrodes provided with a singleuse, replaceable surface can be contemplated.

The stimulating means or as used herein “stimulator” may typicallycomprise a power source configured to generate an electrical current anda controller operatively connected to said power source. The controllermay control the power source to generate electrical current according tothe herein disclosed stimulation parameters to promote contraction ofthe stimulated muscles. The power source may be battery operated, suchthat the device can be freely worn during sleep. The electrodes can beconnected to the stimulator by wires. Exemplary embodiments thereof aredescribed further below.

The bilateral electrodes may provide simultaneous stimulation to theopposite left and right muscles. In some embodiments the providedstimulus along the left and right electrode may be equal. However, inother embodiments the stimulus along the left and right electrode may bedifferent, such that different programs may be programmed according tothe treatment type. The unequal stimulation may be performed usingmultiple controllers or a single controller configured to performseparate stimulations programs for the left and right electrode inaccordance with differences in anatomy; for example a subject having amore defined muscle on one side of the mandible.

The controller may be configured for executing the herein presentedmethods. Embodiments may be implemented in code and may be stored on astorage medium having stored thereon instructions which can be used toprogram a system to perform the instructions. For purposes of thepresent disclosure, the terms “code” or “program” cover a broad range ofcomponents and constructs, including applications, drivers, processes,routines, methods, modules, and subprograms. The terms “code” or“program” may thus be used to refer to any collection of instructionswhich, when executed by a processing system, performs a desiredoperation or operations. Additionally, alternative embodiments mayinclude processes that use fewer than all of the disclosed operations,processes that use additional operations, processes that use the sameoperations in a different sequence, and processes in which theindividual operations disclosed herein are combined, subdivided, orotherwise altered. Those skilled in the art can implement the hereinpresented methods as a code or program and appreciate the numerousmodifications and variations thereon.

The way the generated electrical current is used to transcutaneouslystimulate the targeted muscles can be influenced by multiple factors.The use of continuous low current typically requires less force thanintermittent stimulation as it is easier to maintain an opened upperairway than to initiate the reopening of an occluded airway.Nonetheless, it is beneficial to avoid continuous stimulation forprolonged periods as it may have adverse effects on muscle fatigue andthe sleep quality. Accordingly, selection of the optimal stimulationparameters, including the current intensity (in mA), pulse frequency (inHz), pulse width (in μs), and/or stimulation duration (e.g. continuous,intermittent, triggered), are important factors to promote efficientmuscle response but avoid adverse effects. Additionally, selection ofspecific stimulation parameters may also provoke different physiologicalresponses, specifically, recruiting the muscular fibres, rehabilitatingthe muscle function and retraining the neuromuscular related circuit(through stimulation of the muscles).

The electrical current may be applied in accordance with a regularstimulation pattern having a controlled rhythm to form a pulsed current.In an embodiment the electrical current is a biphasic electrical currentcharacterized by one or more one stimulation parameters, such as thebiphasic current intensity, pulse frequency, pulse width, and/orstimulation duration. Different combinations of signal parameters tendto suit different subjects according to subject specific factors, suchas age, weight, skin type, etc. For example, biphasic current may beparticularly suitable for recruiting, rehabilitating and/or retrainingthe muscles. However, as discussed above certain stimulation parametersrisk inducing muscle fatigue or affecting the sleep quality. Belowvarious stimulation parameters are listed which were found to provide aparticularly good trade-off between high efficacy and risk of sideeffects.

In a general embodiment the current intensity may be selected between atleast 1 mA to at most 50 mA, or 1 mA to 45 mA, or 1 mA to 40 mA, or 1 mAto 35 mA, more preferably 1 mA to 30 mA, or 1 mA to 25 mA, or 5 mA to 25mA, even more preferably 10 mA to 20 mA, or 15 mA to 20 mA, or 10 mA to15 mA.

Variation in signal intensity may affect the muscle contraction force.The stimulation intensity may typically be the first stimulationparameters to be adjusted according to the subject's need and discomfortthreshold.

In a general embodiment the pulse frequency may be selected between atleast 1 Hz to at most 100 Hz, more preferably 10 Hz to 90 Hz, or 10 Hzto 85 Hz, or 10 Hz to 80 Hz, or 15 Hz to 75 Hz, or 15 Hz to 70 Hz, evenmore preferably 20 Hz to 60 Hz, or 25 Hz to 55 Hz, even more preferably30 Hz to 50 Hz, even more preferably about 40 Hz such as 35 Hz to 45 Hz.Variation in signal frequency may affect the muscle contraction force.To achieve appropriate contraction suitable frequency may be selectedwithin the broad range as indicated above and is more suitable withinthe preferred narrow ranges.

In a general embodiment the pulse width may be selected between at least50 μs to at most 1000 μs, preferably 100 μs to 500 μs, or 100 μs to 400μs, more preferably 125 μs to 375 μs, or 150 μs to 350 μs, or 175 μs to325 μs, even more preferably 200 μs to 300 μs, even more preferablyabout 250 μs such as 225 μs to 275 μs. Variation in signal pulse widthmay affect the muscle contraction time. The signal pulse width can alsobe varied according to the subject's need and discomfort threshold.

The stimulation duration may be biphasic such that it consists of tworepeating phases or period, specifically a stimulation period (i.e.,“on” period) that is followed by a stimulation-free rest period (i.e.,“off” period); the difference between the stimulation period and therest defined as the duty cycle. In an embodiment the stimulation periodmay be between at least 1 sec to at most 20 sec, or 1 sec to 15 sec, or1 sec to 10 sec, more preferably 2 sec to 8 sec, even more preferably 3sec to 7 sec, even more preferably 4 sec to 6 sec, even more preferably5 seconds. In an embodiment the rest period may be between at least 1sec to at most 20 sec, or 1 sec to 15 sec, or 1 sec to 10 sec, morepreferably 2 sec to 8 sec, even more preferably 3 sec to 7 sec, evenmore preferably 4 sec to 6 sec, even more preferably 5 seconds. Theduration of the stimulation and rest period may be symmetrical, forexample 5 sec of stimulation followed by 5 sec of rest, or asymmetrical,for example 5 sec of stimulation followed by 10 sec of rest, or 10 secof stimulation followed by 5 sec of rest. The duration and/or relativeratio of the stimulation and rest periods may be adjusted towards aspecific physiological effect. For example, the stimulation period maybe increased and/or the rest period may be decreased to promote musclestimulation. For example, the stimulation period may be decreased and/orthe rest period may be increased to reduce muscle fatigue.

The above specified values provide general guidelines for selection ofone or more stimulation parameters suitable for effectuating aphysiological response from a sleeping subject. However, by selectingmore specific stimulation parameters the physiological response may besteered towards a specific physiological effect. The skilled person mayappreciate that these stimulation parameters may be executed by theherein disclosed wearable stimulation device in the form of executablestimulation programs. At least three different stimulation programs foreffectuating electrical stimulation are contemplated in the presentdisclosure, specifically, recruiting the muscular fibres, rehabilitatingthe muscle function and retraining the neuromuscular related circuit. Itis, however, understood that the wearable device of the presentdisclosure is not limited to only these three different stimulationprograms.

In an embodiment the stimulation for recruiting of the muscular fibres,herein referred to as the “recruitment program”, may comprise atranscutaneous electrical stimulation with a high current intensity at alow frequency with narrow pulse width (relative to the rehabilitationand retraining programs). The recruitment program aims to provide for adirect and acute muscle response with a directly measurable effect forcontrolling the movement of the mandible during a stimulation session,but will typically not provide a persisting effect after the stimulationsession (i.e., when the stimulator is turned off).

The exact parameters of the recruitment program are subject specific;they depend on the subject's physical stimulation response and perceiveddegree of discomfort. In an embodiment the current intensity of therecruiting program may be selected between 5 mA to 10 mA, preferablybetween 6 mA to 10 mA, for example 7 mA, 8 mA or 9 mA. In an embodimentthe frequency of the recruiting program may be selected between 10 Hz to50 Hz, preferably between 15 Hz to 50 Hz, or 20 Hz to 50 Hz, or 25 Hz to45 Hz, or 25 Hz to 45 Hz, or 30 Hz to 40 Hz, for example 30 Hz. In anembodiment the pulse width of the recruitment program may be selectedbetween 25 μs to 300 μs, preferably between 50 μs to 275 μs, 50 μs to250 μs, or 75 μs to 275 μs, or 100 μs to 275 μs, 125 μs to 275 μs, 150μs to 275 μs, 175 μs to 275 μs, 200 μs to 275 μs, or 200 μs to 250 μs;for example 210 μs, 220 μs, 230 μs, 240 μs, or 250 μs.

In an embodiment the stimulation for rehabilitating the muscle function,herein referred to as the “rehabilitation program”, may comprise atranscutaneous electrical stimulation with a low current intensity at alow frequency with narrow pulse width (relative to the recruitment andretraining programs). The rehabilitation program may aim improve themuscle function of the stimulated muscles, e.g. improving thecontractive force and/or reducing the perceived degree of discomfort.The rehabilitation program may provide for an improved muscle responseto the stimulation, which may improve the beneficial effects of thestimulation across multiple, preferably successive sessions.

The exact parameters of the rehabilitation program are subject specific;they depend on the subject's physical stimulation response and perceiveddegree of discomfort, for example if the subject suffered from a muscleor respiratory disease. In an embodiment the current intensity of therehabilitation program may be selected between 1 mA to 4 mA, preferablybetween 2 mA to 4 mA, for example 3 mA. In an embodiment the frequencyof the rehabilitation program may be selected between 10 Hz to 50 Hz,preferably between 15 Hz to 50 Hz, or 20 Hz to 50 Hz, or 25 Hz to 45 Hz,or 25 Hz to 45 Hz, or 30 Hz to 40 Hz, for example 30 Hz. In anembodiment the pulse width of the rehabilitation program may be selectedbetween 25 μs to 300 μs, preferably between 50 μs to 275 μs, 50 μs to250 μs, or 75 μs to 275 μs, or 100 μs to 275 μs, 125 μs to 275 μs, 150μs to 275 μs, 175 μs to 275 μs, 200 μs to 275 μs, or 200 μs to 250 μs;for example 210 μs, 220 μs, 230 μs, 240 μs, or 250 μs.

In an embodiment the stimulation for retraining the neuromuscularcircuit, herein referred to as the “retraining program”, may comprise atranscutaneous electrical stimulation with a low current intensity at ahigher frequency with wide pulse width (relative to the recruitment andrehabilitation programs). The retraining program may aim to retrain theneuromuscular related circuit to alter the central effect of thestimulation on the central drive, i.e., it is directed on the centralneural circuits involved in the breathing activity of the motor branchof the trigeminal nerve from the subject's brain. The retraining programmay achieve a persisting response after the session is terminated oreven discontinued, but may require multiple, preferably successivesession.

The exact parameters of the recruitment program are subject specific;they depend on the subject's physical stimulation response and perceiveddegree of discomfort, for example if the subject suffered from a muscleor respiratory disease. In an embodiment the current intensity of theretraining program may be selected between 1 mA to 4 mA, preferablybetween 2 mA to 4 mA, for example 3 mA. In an embodiment the frequencyof the retraining program may be selected between 50 Hz to 150 Hz,preferably between 60 Hz to 140 Hz, or 70 Hz to 130 Hz, or 80 Hz to 120Hz, or 90 Hz to 110 Hz, for example 100 Hz. In an embodiment the pulsewidth of the retraining program may be selected between 500 μs to 1000μs, preferably between 550 μs to 950 μs, more preferably between 600 μsto 900 μs, even more preferably 650 μs to 850 μs, even more preferably700 μs to 800 μs; for example 750 μs.

The stimulator may be configured to set the intensity of the electricalstimulation according to a stimulation intensity parameter; wherein thestimulation intensity parameter is determined according to thestimulation perception threshold and stimulation discomfort threshold.The current intensity for transcutaneous electrical stimulation may bedependent on the subject's sensitivity threshold and habituation. Theoptimal stimulation intensity may provide for a user personalizedprogram to accommodate for subject specific parameters, such asvariances in skin conductivity, muscle thickness, fat or adipose tissuethickness, and the like. In an embodiment, the current intensity of theelectrical stimulation is adjusted to a value between the stimulationperception threshold and stimulation discomfort threshold. For example,the current intensity may be set halfway between the stimulationperception threshold and the stimulation discomfort threshold, i.e.,half (%) of the sum of the stimulation perception threshold (in mA) andthe stimulation discomfort threshold (in mA). Alternatively, the currentintensity parameter may be set to quarter (K) or three quarters (Y)between the stimulation perception threshold and the stimulationdiscomfort threshold according to the treatment type.

The stimulation intensity parameter may be determined via user input. Inan embodiment, the stimulator may be configured for connecting to aninput device, such as a smartphone, and receiving subject specific inputfrom said input device. The input device may prompt the user to enter astimulation perception threshold, which corresponds to the lowestintensity of the electrical stimulation at which the subject stillperceives the electrical stimulation to promote contraction of thetargeted muscles, and a stimulation discomfort threshold, whichcorresponds to the highest intensity of the electrical stimulation atwhich the subject perceives a degree of discomfort due to the pulsedelectrical current, such as muscle pain, which could potentially affectthe sleep quality.

The stimulator may be provided with a stimulation intensitydetermination programme configured to automatically determine theoptimal stimulation intensity parameter. For example, the stimulator mayset a predefined intensity based on subject specific parameters, such asage or sex, then gradually increase the current until the subjectreports the occurrence of a perceived discomfort event, and thengradually decrease the current until the subject reports the lack ofperceived stimulation. The stimulator may then calculate an optimalstimulation intensity parameter based on the reported discomfort andperception thresholds. Alternatively, the stimulator may also beselectively operable by a user to apply a stimulation intensityaccording to the user input. This may allow the user to quickly set-upthe device if the optimal intensity parameter is already known, forexample from a previous session. The skilled person may appreciate thata detection programme may also be provided for other stimulationparameters, such as the pulse frequency or width.

The stimulator may be configured to selectively increase the electricalstimulation intensity according to device and/or user feedback. Repeatedsessions of transcutaneous electrical stimulation may reduce the muscleresponse overtime thereby increasing the stimulation perceptionthreshold. Also, the subject may also become habituated to theelectrical stimulation thereby increasing the stimulation discomfortthreshold. To avoid the need for user recalibration, the stimulator maybe configured to automatically adjust the stimulation intensity betweenat least two sleeping session. Preferably, the stimulation intensity thestimulation intensity is adjusted between each and every consecutive twosleeping sessions. Alternatively, the stimulation intensity may beadjusted when specific treatment goals are met, such as a % reduction insnoring intensity or % increase in muscle strength. In an embodiment,the stimulator may automatically increase the stimulation intensity by afixed rate, for example an increase of 1% to 25% with each sleepingsession. Alternatively, the user may be prompted to manually adjust thestimulation intensity.

The stimulator may be configured to apply a pre-stimulation electricalcurrent to improve the stimulated muscle response to the transcutaneouselectrical stimulation. In particular, the stimulator may be configuredto apply a time-limited high frequency electrical current from the leftand/or right electrode to the subject skin to reduce the skin impedance.Skin typically presents a certain resistivity to the passage of thecurrent which may be expected to decrease after a certain time. However,the electrical skin impedance of certain subject groups having moreresistive skin, such as elderly or coloured, may require substantiallymore time for the skin resistivity drop to occur. Moreover, highresistivity means that the current is primarily established on the skinsurface and generates unpleasant sensations.

It is therefore beneficial to reduce the skin impedance by performingpre-stimulation protocol to reduce skin impedance and ensure properresponse of the muscle to the electrical stimulation. Thepre-stimulation protocol may, for example, be applied when the device isfirst activated and/or right before a subject enters a targeted sleepcycle. In an embodiment the pre-stimulation protocol may be apre-stimulation current with a low pulse width and high frequency(according for the power supply capabilities and subjects perceiveddiscomfort threshold) for a limited time, such as one to five minutes.For example, the pre-stimulation current may be current with a pulsewidth of 100 μs and a pulse frequency of 100 Hz for which is applied bythe electrode for one to two minutes.

The stimulator may determine and adjust the stimulation parameters viapre-set programmes provided on a memory device of the stimulator.Adhering to a pre-set programme may be suitable for embodiments whereincontinuous stimulation is desired across the entire sleep cycle.Nonetheless, the stimulator may also be configured to providestimulation based on data by a sensing unit.

The purpose of masseter, pterygoid and/or temporalis muscles stimulationis to position the jaw in such a way that normal breathing is realisedand the respiratory effort is decreased. Hence, for optimal stimulationthe electrode should advantageously be placed onto these muscles.Identification of these muscles can be difficult, especially for anon-medically trained subject for at home use of the wearable device.Nonetheless, a method for positioning of the electrodes on thesuperficial masseter and anterior temporalis muscles can be formulatedbased on the anatomical landmarks, specifically the zygomatic arch (Za)and gonial angle (Go). By using anatomical landmarks as references, agreater reproducibility can be ensured for positioning electrodes overthe targeted muscles. Reproducibility of electrodes positioning may beadvantageous for longitudinal stimulation to ensure the stimulation of aparticular muscular portion location (spatial distribution of motor unitaction potentials are not uniform through the whole extension of amuscle).

In an embodiment, a method for placement of electrodes on the massetermay comprise the steps of:

-   -   (i) identifying the gonial angle, preferably the corner angle of        the mandible;    -   (ii) identifying the zygomatic arch, preferably the outer corner        of the eye;    -   (iii) identifying the masseter muscle extending from said gonial        angle towards said zygomatic arch;    -   (iv) identifying a target stimulation zone on said masseter        muscle, preferably ranging from the gonial angle up to halfway        the distance between the gonial angle and the zygomatic arch        along the muscle fibre direction.    -   (v) optionally, placing an electrode according to the present        disclosure on said target stimulation zone.

In an embodiment the electrode the electrode is a bipolar electrodecomprising two conductive surfaces, wherein the first electricallyconductive element is mounted on the masseter muscle's motor point,preferably adjacent to the gonial angle, and the second electricallyconductive element is mounted along the direction of the masseter musclefibre, preferably halfway the distance between the gonial angle and thezygomatic arch along the muscle fibre direction. An example of themethod for placement of an electrode on the masseter muscle isillustrated in FIG. 9 .

Advantageously, the electrode can be placed on the muscle belly, themidpoint of a muscle or along the muscle fibres direction, as determinedby palpation or visual observation. Nonetheless, different tissuesbetween the electrodes-muscle interface present anisotropiccharacteristics, therefore it is desirable that electrodes are placed atthe same direction as muscle fibres. This may allow a pair of electrodesto pick up a spread of action potentials from the same bundle of musclefibres, and thus, of corresponding muscle volumes to promote stimulationefficiency.

Advantageously, the surface electrode can be placed along the musclefibres, over the most prominent region at the moment of musclecontraction. Preferably, the electrode surface may be placed to be nearthe main motor neuron of the muscle (close to motor point of the muscle)such that the energy can dispatch along the length of the fibre,conducted by the axon of the motor neuron from the main motor point. Bytransferring the energy directly to the motor neuron, the electrode canreduce the dissipation of electric currents through the skin (thedermis) to other muscles of the head (e.g. orbicularis, labialis, etc.)that could contract and elevates the eyelid or the lip and otherssensory endings causing discomfort such as paraesthesia.

It may be appreciated that the exact anatomy of the target muscles isunique and hence differs between subjects. Thus, any recommendation forsurface electrodes positioning based on anatomical landmarks that arenot closely related to the muscles of interest, or are notindividualized, would not respect the precept that electrodes canadvantageously be placed parallel to muscle fibres and over its largestvolume. Surface electrodes, in a bipolar configuration, mayadvantageously be placed between the innervation zone and the tendinousinsertion, depending directly on the anatomy of the muscle to bestimulated. The innervation zones of masseter, pterygoid and/ortemporalis are typically widely dispersed, hampering electrodesplacement over the recommended optimal anatomical region. Surfaceelectrodes may be placed on one or two different locations that arebased on easily palpable (use of palpation during muscle contraction)and specific anatomical references/landmarks (zygomatic arch and gonialangle) to guide the subject in their routine and guarantee the qualityof the stimulation. This may further promote stimulation efficiency andreduce discomfort due to regional side effects.

The sensing unit or as used herein “sensor” may record data related tovarious activities of the subject, such as respiratory activity/effortand/or stimulation response. After recording, the sensing data may beprocessed by a processing unit, specifically a data analysis unit thatis operatively connected to the stimulator, for example via a data link,or alternatively is part of the stimulator, such as the controller.

This stimulator may for this purpose be adapted to receive feedback fromthe data analysis unit in the form of instructions to adjust thestimulation. The data link may be a wired or wireless connection.

Advantageously the sensor may be mounted on at least one electrode ofthe wearable device, such that the stimulation effects can be directlymonitored. Nonetheless, the sensor may also be provided on another partthe subject, such as the chin or chest, depending on which activity isto be measured and the degree of sensitivity. Below embodiments ofsensors are contemplated that may be particularly suitable incombination with the present device for transcutaneous stimulation ofthe target muscles.

Advantageously, the sensing unit may be integrated into the wearabledevice for providing a transcutaneous electrical stimulation to musclescontrolling the movement of the mandible of a subject to decrease therespiratory effort of said subject during sleep and/or prevent theoccurrence of sleep respiratory disturbances. This has the advantagethat data can be recorded during stimulation, reducing the chance forpossible time delay or mismatching of stimulation programs. Also, thewearable device for monitoring and/or analysing respiratory activity ofa sleeping subject may comprise an integrated sensing unit. Also, thewearable devices for monitoring and/or analysing sleeping activity of asleeping subject may comprise an integrated sensing unit.

The wearable devices of the present disclosure may comprise a sensingunit configured for recording of mandibular and/or head movement of thesubject and recording said movements as mandibular activity data thatincludes one or more mandibular features, such as a position, rotationor displacement of the subject's mandible and/or one or more headfeatures, such as a position, rotation or displacement of the subject'shead.

In an embodiment the mandibular activity data may also provideinformation on stimulation efficacy, specifically the muscle response ofthe subject to the applied stimulation, which may be determined fromderived mandibular features such as displacement of the mandible and/orhead during sleep or changes in respiratory effort and/or central drive.

In an embodiment the mandibular activity data may also provideinformation on muscle fatigue of the subject, which may be determinedfrom derived mandibular features such as displacement of the mandibleand/or head during sleep or changes in respiratory effort and/or centraldrive.

In an embodiment the mandibular activity data may also provideinformation on snoring or sleep related noises and/or the generalsleeping quality of the subject, which may be linked to mandibularfeatures such as displacement of the mandible and/or head during sleep.

In an embodiment the sensing unit may be configured for recording ofmandibular movement and a processing unit operatively connected to saidsensing unit; wherein the processing unit is configured to receive, fromsaid sensing unit, mandibular activity data; and, determine, from themandibular activity data one or more respiratory features which areindicative of respiratory activity of the subject and/or one or moresleeping features which are indicative of a sleeping activity of thesubject. The inventors have determined that mandibular data may belinked to respiratory and/or sleeping parameters, for example directlythrough by threshold-based detection of specific derived mandibularactivity features or indirectly by pattern recognition of mandibularactivity data. Exemplary embodiments of such configurations may be founddiscussed further below.

The sensor may comprise at least one gyroscope configured for recordingrotational movements of the subject's mandible. The recorded rotationalmovements data may be linked to various mandible movement classescomprising a set of rotational values, which may be indicative of atleast one rate, rate change, frequency, and/or amplitude of mandibularrotations associated with the mandible movement class. The recordedrotational movements may be analysed to determine mandibular activitydata, respiratory activity data and/or sleeping activity data asdescribed above. Advantageously, the gyroscope is provided on the leftand/or right electrode such that it can be placed together with theelectrodes and reduce the complexity of the device.

The provision of a gyroscope in the sensing device was found to beparticularly well suited for recording of mandibular movement incomparison to other sensing devices typically applied in the art, suchas accelerometers, force/pressure sensors, or magnetic sensors. Forinstance, an accelerometer can only allow for measurement of linearacceleration and is thus unsuitable for measurement of rotationalmandibular displacements. Moreover, the accelerometer can be affected bymovement of the body or the head, such as the chest or trachea duringbreathing, and distinguishing between the origin of data is difficultand adds unnecessary noise and complexity to the system. This has anegative impact on a diagnosis that is based on the measured datastreams. The inventors have found that the rotation of the mandible asrecorded by a gyroscope carries the necessary information to arrive atan accurate assessment of mandibular activity data, respiratory activitydata and/or sleeping activity data as described above.

In a preferred embodiment the sensing device may comprise at least onegyroscope, at least one accelerometer and optionally also at least onemagnetometer. The inventors have found that accelerometers areparticularly well-suited for measuring movements and positions of thehead. The addition of an accelerometer to the present system may allowto discern head movement from jaw movement and thereby more accuratelyassess the behaviour of the mandible during sleep. Further, theprovision of a magnetometer may allow assessing the orientation of thesensing unit like a compass to determine the direction of the movementsrecorded by the gyroscope and/or accelerometer. Accordingly, thepreferred embodiment may be particularly well suited for recording ofmandibular movement.

In some embodiments the sensor may also comprise devices selected fromthe list including an oxygen sensor (e.g. oximeter), a temperaturesensor (e.g. thermometer), a sound sensor (e.g. microphone), a muscleactivity sensor (e.g. electromyography unit), a brain activity sensor, aheart activity sensor, a blood sensor (e.g. pulse photoplethysmography).The provision of additional sensing devices may allow for the sensor tobe customised to patient specific purposes, such as the detection ofsnoring.

Additionally, the wearable device as described herein may also be usedin combination with other systems or methods. These systems may betherapeutic in nature, such as a breathing apparatus (CPAP, BiPAP,Adaptive Support Ventilation), a device for stimulating specific nervesand/or other muscles, whether transcutaneous or implanted, a device forcorrecting the posture and/or position of the body and/or head duringsleeping. In some embodiments an alarm can be coupled to the system,and/or the system may be connected to or provided with a device havingan alarm function.

The wearable devices of the present disclosure may comprise a processingunit, also referred to as data analysis unit, configured to receive,from said sensing unit, mandibular activity data; and, determine, fromthe mandibular activity data, one or more mandibular features, such as aposition, rotation or displacement of the subject's mandible and/or oneor more head features, such as a position, rotation or displacement ofthe subject's head.

In an embodiment the wearable device may comprise a sensing unitconfigured for recording of respiratory activity of the subject and aprocessing unit operatively connected to said sensing unit; wherein theprocessing unit is configured to receive, from said sensing unit,respiratory activity data; and, determine, from the respiratory activitydata, one or more respiratory features, such as the frequency orintensity of the breathing, the occurrence of sleep disturbed breathingmarked with increased respiratory effort and/or the occurrence of arespiratory disturbance, such as airway obstruction or collapse.

In some embodiments the respiratory activity data may also provide thedevice with feedback on the efficacy of the stimulation but may alsotrigger the device to initiate specific programmes to treat respiratorydisturbances. In a particular embodiment the respiratory activity datamay also provide information on snoring of the subject, which may belinked to respiratory features such as an increase in respiratory effortduring sleep.

The wearable device may comprise a sensing unit configured for recordingof sleeping activity of the subject and a processing unit operativelyconnected to said sensing unit; wherein the processing unit isconfigured to receive, from said sensing unit, sleeping activity data;and, determine, from the sleeping activity data, one or more sleepingfeatures, such as sleeping state detection, determination of specificsleeping stages and/or assess the sleep quality. The sleep activity datamay provide the device with feedback on the efficacy of the stimulationbut may also trigger the device to target specific sleeping states orstages. The sleep quality parameters may include, e.g., total sleep time(TST), sleep onset latency (SOL), wake time after sleep onset (WASO),awakening or arousal index, sleep efficiency (SE), ratios of REM,non-REM sleep, REM sleep latency, and other sleep quality metrics.

The data analysis unit may be configured to derive a plurality of valuesfrom one or more sensing data as described above, such as the mandibularactivity data, respiratory activity data and/or sleeping activity data,and for matching the derived values with predefined classes. Preferably,the sensing data is sampled with a specific sampling rate, which may forexample range from 1.0 to 100.0 Hz, or from 2.0 to 50.0 Hz, or from 5.0to 25.0 Hz, preferably 10.0 Hz. The values from the sampled or unsampledsensing data may comprise one or more of the following mathematicalprocedures: discretization, time-averaging, normalisation, (fast)Fourier transformation, and the like. Those skilled in the art mayappreciate the numerous modifications and variations thereon.

The matching may be fully or partially automated by the provision of amachine learning model, such that the data analysis unit is configuredto learn a number of statistical and/or physical metrics in order tocapture the characteristics of the signal in frequency and time domainsand identify patterns of rotation signal to specific events, such assleep stages, respiratory effort, muscle fatigue, and the like. In anembodiment the machine learning model may be selected from the list ofextreme gradient boosting, deep neural network, convolutional neuralnetwork, random forest. The inventors found that these models areparticularly suited for classifying the recorded mandibular activitydata, respiratory activity data and/or sleeping activity data into thecorresponding classes. However, those skilled in the art may appreciatethe numerous modifications and variations thereon. The provision of amachine learning model may thus provide for automatic interpretation ofthe relevant information and/or matching characteristic data with sleepdisorder events.

In an embodiment the data analysis unit, preferably by means of recordedmandibular activity data, may be configured to determine efficacy of thestimulation without requiring subject feedback, specifically duringsubject sleep. High efficacy of the stimulation can be determined whenirregular movement of the mandible decreases over time, preferablysynchronises with the selected stimulation parameters of the appliedelectrical stimulation. On the other hand, a high occurrence ofirregular mandibular movement may indicate that the muscles of thesubject are not sufficiently responding to the applied electricalstimulation and as such one or more stimulation parameters may need tobe adjusted, for example by increasing the current intensity.

In an embodiment the sensing unit, preferably by means of recordedmandibular activity data, may be configured to determine muscle fatiguewithout requiring subject feedback, specifically during subject sleep.Muscle fatigue can be determined when the elevation of the mandibledecreases overtime, yet the stimulation parameters remained unchangedacross a specific period of time or sleeping stage.

In an embodiment, muscle fatigue can be more accurately determined bytracking the displacement of the mandible, preferably by means of anaccelerometer, and/or by tracking the central drive and/or respiratoryeffort, preferably by means of a gyroscope. An embodiment of a sensingunit comprising an accelerometer and gyroscope, preferably mounted onthe same position, is therefore contemplated.

In an embodiment, the following parameters may allow for determiningtypes of muscle fatigue:

-   -   Absence of muscle fatigue may be determined when distinct mouth        closing can be observed (typically in the form of distinct        mandible displacement in recorded accelerometer data) and/or the        central drive/respiratory effort is decreasing (typically        derived from the peak-to-peak amplitude of recorded gyroscope        data).    -   Peripheric muscular and/or fibre fatigue may be determined when        distinct mouth closing cannot be observed (typically reduced        mandible displacement in the recorded accelerometer data) and/or        the central drive/respiratory effort is increasing (typically        indicated by increased peak-to-peak amplitude of the recorded        gyroscope data).    -   Spinal or supraspinal fatigue may be determined when distinct        mouth closing cannot be observed (typically reduced mandible        displacement in the recorded accelerometer data) and/or the        central drive/respiratory effort is decreasing (typically        indicated by decreased peak-to-peak amplitude of the recorded        gyroscope data).

Analysis of the recorded data may be used to provide a feedback loop forthe wearable device to improve control of the subject's mandible byadjusting one or more stimulation parameters and advantageously improvethe device efficacy. In an embodiment the wearable device may comprise aprocessing unit which is operatively connected to the stimulator andconfigured to determine from the sensing data a stimulation response andcompare said stimulation response with a desired response. Further, theprocessing unit may be configured to adjust at least one electricalstimulation parameter if a difference between the stimulation responseand desired response is determined to effectuate the desired response oralternatively determine an adjustment to least one electricalstimulation parameter to effectuate the desired response and provide thestimulator with said adjustment as instructions. In an embodiment thestimulation intensity may be adjusted. Nonetheless, the pulse frequency,the pulse width and/or the stimulation duration may also be adjusted.Exemplary embodiments of respiratory feedback loops may be founddiscussed below.

In an embodiment the processing unit may be configured to determine frommandibular activity data the mandibular response to the stimulation andcompare said mandibular stimulation response with a desired response,the desired response consisting of an elevation of the subject'smandible to open the upper airway. In an embodiment the processing unitmay be configured to determine from respiratory activity data thestimulation response and compare said respiratory stimulation responsewith a desired response, the desired response consisting of a decreasein the respiratory effort of a sleeping subject. In an embodiment theprocessing unit may be configured to determine from sleeping activitydata the sleeping response to the stimulation and compare said sleepingstimulation response with a desired response, the desired responseconsisting of an improvement in the sleeping quality of a sleepingsubject. Additionally, the device may be configured for determination ofother responses, such as reduction in snoring.

Analysis of mandibular activity data may be used to track musclefatigue. The wearable device may be provided with a muscle fatiguedetection module which is configured to determine muscle fatigue in thesubject's mandibular activity data and preferably adjust one or morestimulation parameters of the electrical stimulation. There aredifferent stimulation parameters that can be adjusted, individually orin combination, to adjust neuromuscular electrical stimulation foroptimized benefits, specifically improve closure of the mouth and/orreduce or prevent muscle fatigue. These parameters may include thecurrent intensity, the pulse width and frequency, the duty cycle,stimulation of different target muscles, sequential periods ofstimulation as a function of the target, target of specific period oftime or a sleeping stage, amplitude of the monitored accelerometer anddrive responses. For example, if muscle fatigue is detected, it possibleto reduce the current intensity, preferably by 10%, 20%, 30%, 40%, 50%or more, and/or modify the duty cycle, specifically by increasing therest period of the duty cycle, preferably by 10%, 20%, 30%, 40%, 50% ormore; for example from 5 sec to 10 sec. Alternatively, upon detection ofmuscle fatigue the detection module may temporarily interrupt theelectrical stimulation to allow the muscles to recover, for example byproviding a break for 1 min or 2 min. Once the stimulation is restartedthe muscle fatigue detection module may determine if the stimulationresponse has improved and if there is insufficient improvement provideanother, preferably longer break.

In an embodiment the muscle fatigue detection module may be configuredto change one or more stimulation programs when a specific sleepingstage is detected, specifically the recruitment program, therehabilitation program and/or the retraining program. The session may betypically initiated with the recruitment program and/or therehabilitation program. However, since these programs may fatigue themuscles (due to relatively narrow pulses and/or higher currentintensity), the muscle fatigue module may be configured to switch thestimulator to the retraining program (with relatively wider pulsesand/or lower current intensity) in order to reduce the muscle fatigue,for example when central fatigue is detected.

In an embodiment the muscle fatigue detection module may be configuredto determine the type of muscle fatigue, specifically periphericmuscular and/or fibre fatigue, and/or spinal or supraspinal fatigue. Themethodology of muscle fatigue detection is discussed earlier in thepresent disclosure. In an embodiment the muscle fatigue detectionmodule, when detecting peripheric muscular and/or fibre fatigue, mayreduce the current intensity and/or increase the pulse width of thesimulation, preferably by activating a program defined by a lowercurrent intensity and/or wider pulses than the present program. In anembodiment the muscle fatigue detection module, when detecting spinal orsupraspinal fatigue, may increase the frequency and/or increase thepulse width of the simulation, preferably by activating a programdefined by a higher frequency and/or wider pulses than the presentprogram.

In a particular embodiment, the processing unit may be configured todetect poor muscle contraction and adjust the session to commence withthe rehabilitation program. To clarify, in the presence of a milddisease with no severe episodes of apnea or hypopnea, there is time torehabilitate the target muscles. Accordingly, instead of adjusting oneor more stimulation parameters to increase the efficiency of theelectrical stimulation (e.g. by increasing current intensity and/orfrequency), it may be preferably to decrease the electrical stimulatesuch that the muscle fibre strength can built up to take the strongerstimulation. This may alleviate discomfort for subjects at risk ofmuscular fatigue or highly sensitive to higher current intensities todiscontinue the session. Advantageously, this functionality may beincluded in the wearable device to be activated on demand, for examplewhen a clinical physician diagnoses poor masseter contraction or someunderling disease. Also, the rehabilitation program can be proposed tosubject sensitive to current intensities above 2 mA, specifically whenthe stimulation prevents the subject from falling asleep and/or wakes upthe subject after a ramp period.

The wearable device may be provided with a respiratory effort detectionmodule which is configured to determine the level of respiratory effortin the subject's respiratory data. In an embodiment the respiratoryeffort detection module may be configured to detect an increasedrespiratory effort in the subject's respiratory data and adjust one ormore stimulation parameters and/or stimulation programs to reducerespiratory effort. Stimulation can be adjusted based on recordedrespiratory effort/central drive; preferably by increasing theefficiency of the stimulation when an increase in respiratoryeffort/central drive is detected, and/or by decreasing the efficiency ofthe stimulation when a decrease in respiratory effort/central drive isdetected.

In an embodiment the respiratory disturbance detection module may beconfigured to detect a higher frequency and/or higher amplitude(peak-to-peak amplitude) indicative of increased respiratory effort,preferably compared to a baseline value, and adjust one or morestimulation parameters to promote stimulation; preferably by maintainingthe same frequency and pulse width but increasing the current intensity;more preferably by increasing the current intensity by 10%, 20%, 30%,40%, 50% or more, and/or decrease the rest period of the duty cycle by10%, 20%, 30%, 40%, 50% or more. This may improve the stimulation'sefficiency and/or reduce respiratory effort/central drive. The baselinevalue may be a standard value, for example based on an expectedpopulation average, but preferably is a personalised value based on thesubject's respiratory profile. Advantageously the baseline value startsoff as a standard value during the start of a session and is adaptedbased on recorded data.

In an embodiment the respiratory disturbance detection module may beconfigured to detect a lower frequency and/or lower amplitude(peak-to-peak amplitude) indicative of decreased respiratory effort,preferably compared to a baseline value and adjust one or morestimulation parameters to reduce stimulation; preferably by maintainingthe same frequency and pulse width but decreasing the current intensity;more preferably by decreasing the current intensity by 10%, 20%, 30%,40%, 50% or more, and/or increasing the rest period of the duty cycle by10%, 20%, 30%, 40%, 50% or more. This may improve the subject's comfortand/or reduce the chance for muscle fatigue.

Analysis of respiratory activity data may be used to selectively focus aspecific respiratory disturbance, such as airway obstruction orcollapse. The wearable device may be provided with a respiratorydisturbance detection module which is configured to determine thepresence of a respiratory disturbance in the subject's respiratory datasuch that the electrical stimulation can be initiated or adjusted when arespiratory disturbance is detected. Stimulation can be adjusted basedon the detection of a respiratory disturbance, such as airwayobstruction or collapse; preferably by increasing the efficiency of thestimulation when an increased amplitude, frequency and/or duration ofone or more respiratory disturbances is detected, and/or decreasing theefficiency of the stimulation when a decreased amplitude, frequencyand/or duration of one or more respiratory disturbances is detected.

In an embodiment the respiratory disturbance detection module may beconfigured to detect a higher frequency, higher amplitude (peak-to-peakamplitude) and/or increased duration of respiratory disturbancescompared to a baseline value and adjust one or more stimulationparameters to promote stimulation; preferably by maintaining the samefrequency and pulse width but increasing the current intensity; morepreferably by increasing the current intensity by 10%, 20%, 30%, 40%,50% or more, and/or decrease the rest period of the duty cycle by 10%,20%, 30%, 40%, 50% or more. This may improve the stimulation'sefficiency and/or reduce, preferably prevent, the occurrence of furtherrespiratory disturbances. The baseline value may be a standard value,for example based on an expected population average, but preferably is apersonalised value based on the subject's respiratory profile.Advantageously the baseline value starts off as a standard value duringthe start of a session and is adapted based on recorded data.

In an embodiment the respiratory disturbance detection module may beconfigured to detect a lower frequency, lower severity and/or decreasedduration of respiratory disturbances compared to a baseline value andadjust one or more stimulation parameters to reduce stimulation;preferably by maintaining the same frequency and pulse width butdecreasing the current intensity; more preferably by decreasing thecurrent intensity by 10%, 20%, 30%, 40%, 50% or more, and/or increasingthe rest period of the duty cycle by 10%, 20%, 30%, 40%, 50% or more.This may improve the subject's comfort and/or reduce the chance formuscle fatigue.

Analysis of respiratory activity data may be used to selectively focussnoring and/or sleep related noises. The wearable device may be providedwith a snoring detection module which is configured to determine theoccurrence of snoring/sleep related noises such that the electricalstimulation can be initiated or adjusted when snoring/sleep relatednoises is detected. The snoring detection may optionally be thresholdbased, for example when exceeding a specific volume. Stimulation can beadjusted based on recorded snoring or sleep related noises; preferablyby increasing the efficiency of the stimulation when an increase insnoring/sleep related noises is detected, and/or by decreasing theefficiency of the stimulation when a decrease in snoring/sleep relatednoises is detected; preferably by maintaining the same frequency andpulse width but increasing the current intensity; more preferably byincreasing the current intensity by 10%, 20%, 30%, 40%, 50% or more,and/or decrease the rest period of the duty cycle by 10%, 20%, 30%, 40%,50% or more. This may improve the stimulation's efficiency and/orreduce, preferably prevent, the occurrence of further snoring/sleeprelated noises.

The wearable device may be provided with a sleeping stage determinationmodule which is configured to determine an awake and asleep state of thesubject such that the electrical stimulation can be initiated when thesubject falls asleep and terminated as the patient wakes up. Theelectrical stimulation may be perceived as distractive for fallingasleep by certain subjects. The detection of at least an awake andasleep phase allows the subject to fall asleep more easily before thestimulation is initiated. Also, the electrical stimulation may begradually initiated to avoid from awakening the subject due toactivation of the device, for example by gradually increasing thestimulation intensity.

The wearable device may be provided with a sleeping stage determinationmodule which is configured to determine one or more sleep stages of thesubject such that the electrical stimulation can be initiated, adjustedand/or terminated when the subject enters a specific sleeping stage.Accurate sleeping state detection may improve the stimulation responseand hence the efficiency of the sessions for therapeutic ornon-therapeutic purposes. Further, accurate sleeping stage detection mayincrease the safety and comfort of the session, specifically by reducingor preventing stimulation during deep sleep (e.g. N3) and/or duringawake states or awakenings. This allows the device to focus a specificsleeping stage of the subject for stimulation such that the subject canstill fall easily asleep or does not wake during the deeper stages.Further still, accurate sleeping state detection may reduce or preventthe occurrence of muscle fatigue, specifically by reducing or preventingstimulation during specific deep sleep (e.g. N3) and/or providing avariable stimulation during lighter sleep, for example by progressivelyincreasing/decreasing the current intensity.

The sleep detection module may be configured to detect a specific sleepstage according to the following classification (sorted by increasinglevel of computational complexity):

-   -   2 Class (i.e. binary) scoring for detecting the awake or        sleeping state in a subject;    -   3 Class scoring for classifying the sleeping stage, including        the awake state, the light sleeping (N1 and N2) stage and/or the        non-light sleeping (N1 and N2) stage in a subject;    -   3 Class scoring for classifying the sleeping stage, including        the awake state, the deep sleeping (N3) stage and/or the        non-deep sleeping (N3) stage in a subject;    -   3 Class scoring for classifying the sleeping stage, including        the awake state, the REM sleeping stage and/or the non-REM        sleeping stage in a subject;    -   4 Class scoring for classifying the sleeping stage, including        the awake state, the light sleeping (N1 and N2) stage, the deep        sleeping (N3) stage and/or the REM sleeping stage in a subject;    -   5 Class scoring for classifying all sleeping stages, including        the awake state, the N1 sleeping stage, the N2 sleeping stage,        the N3 sleeping stage and/or the REM sleeping stage in a        subject.

The skilled person may appreciate that, depending on the required dataprocessing complexity, the data analysis may be performed by theprocessing unit provided on the wearable device or, if more complexcalculation is required, the calculation may be performed on an externaldevice that is connected to the wearable device, such as the subject'ssmartphone or a server. Nonetheless, for the sake of convenience in thepresent disclosure it will be assumed that all necessary calculationscan be performed by the sleeping stage determination module as disclosedherein.

In an embodiment the sleeping stage determination module may beconfigured to determine the occurrence of a light sleeping (N1 and/orN2) stage and/or REM stage and initiate or adjust the applied electricalstimulation when the subject enters said light sleeping (N1 and/or N2)stage and/or REM stage. It was discovered that during the light sleeping(N1 and/or N2) stage, the muscles are more sensitivity for retrainingpurposes and as such may benefit for an adjustment to one or morestimulations parameters, such as an increased stimulation intensity. Thelight sleeping (N1 and/or N2) stage and/or REM stage may be associatedwith a specific mandibular condyle rotation and may therefore bedetermined from mandibular activity data. Moreover, during lightsleeping (N1 and/or N2) stage and during REM sleep stage, the risk ofapnea/hypopneas increases (in comparison to the deep N3 sleep stage),essentially because the compensatory drive directed to the pharyngealmusculature is reduced or highly variable and thus less efficient (REMsleep).

The N3 sleeping stage is typically characterized by stable mandibularmovements. Accordingly, in an embodiment the sleeping stagedetermination module may be configured to determine N3 based on a stablepeak-to-peak amplitude and/or breathing frequency. After detection ofthe N3 sleeping stage the sleeping stage determination module may beconfigured to switch to the rehabilitation program; preferably bymaintaining the same frequency and pulse width but decreasing thecurrent intensity; more preferably by decreasing the current intensityby 10%, 20%, 30%, 40%, 50% or more, and/or increasing the rest period ofthe duty cycle by 10%, 20%, 30%, 40%, 50% or more. Alternatively, afterdetection of the N3 sleeping stage the sleeping stage determinationmodule may be configured to switch to the retraining program; preferablyby increasing the frequency and pulse width and optionally decreasingthe current intensity; preferably by increasing the frequency by 10%,20%, 30%, 40%, 50% or more, increasing the pulse width by 10%, 20%, 30%,40%, 50% or more, increasing the rest period of the duty cycle by 10%,20%, 30%, 40%, 50% or more and/or decreasing the current intensity by10%, 20%, 30%, 40%, 50% or more.

The REM sleeping stage is typically characterized by unstable mandibularmovements. Accordingly, in an embodiment the sleeping stagedetermination module may be configured to determine REM based on anunstable peak-to-peak amplitude and/or breathing frequency. Afterdetection of the REM sleeping stage the sleeping stage determinationmodule may be configured to switch to the recruitment program;preferably by maintaining the same frequency and pulse width butincreasing the current intensity; more preferably by increasing thecurrent intensity by 10%, 20%, 30%, 40%, 50% or more, and/or decreasethe rest period of the duty cycle by 10%, 20%, 30%, 40%, 50% or more.Alternatively, if the stimulator is already operating in the recruitmentprogram, one or more parameters of said recruitment program may beadjusted to increase stimulation; preferably by increase the currentintensity by 10%, 20%, 30%, 40%, 50% or more, and/or decrease the restperiod of the duty cycle by 10%, 20%, 30%, 40%, 50% or more.

In an embodiment the sleeping stage determination module may beconfigured to slowly ramp up during the during the N1 sleep stage inanticipation of the following sleep stages to prevent the occurrence ofinappropriate arousals. In adults, the typical N1 sleeping stage is arelatively short and light; the sleep stage may be expected to deepen ina few minutes. Accordingly, the sleeping stage determination module maybe configured according to a ramping algorithm that detects an amount ofpredefined amount of continuous sleep, preferably by means of thesleeping stage sensor as disclosed herein. Once a specific sleep stagehas been detected, the ramping algorithm may adjust one or morestimulation parameters over a specific time length, for example bylinearly increasing the current intensity from 0% to 100% over 20minutes.

In an embodiment the sleeping stage determination module may beconfigured to determine the occurrence of a deep sleeping (N3) stage andterminate the applied electrical stimulation when the subject enterssaid deep sleeping (N3) stage. It was discovered that during the deepsleeping (N3) stage, the risk of incident and severe SDB decreasesbecause the central motor control of the ventilation is stabilised atthe lever of the upper airway muscles (stability of the chemo and barodrive) and the upper airway patency (through the premotor neurons of theV, XII and VII cranial nerves) is optimized by the neurons regulatingbreathing. Accordingly, the electrical stimulation can be reduced oralternatively terminated the during the deep sleeping (N3) stage, whichmay allow the stimulated muscles to relax in order to prevent musclefatigue. The deep sleeping (N3) stage may also be associated with aspecific mandibular condyle rotation and may therefore be determinedfrom mandibular activity data.

In an embodiment the sleeping state or stage of the subject may bedetermined by the following programme:

-   -   dividing the sensing data into epochs of a specific time, for        example 30 seconds, wherein the sensing data is preferably        selected from mandibular activity data, respiratory activity        data and/or sleep activity data, and    -   applying a mathematical model to assign a sleeping state to each        epoch;    -   wherein said mathematical model comprises the step of    -   extracting at least one feature from the recorded sensing data        for each epoch;    -   tracking the value of said extracted feature across every epoch;    -   setting a feature specific threshold value; and,    -   adjusting the sleeping state of an epoch if the extracted        feature value exceeds the feature specific threshold value.

Typical features extracted by the sleep detection model from therecorded sensing data may include the maximum and minimum values (e.g.mandibular activity data recorded by a gyroscope), the mean, the median,the standard deviation. Preferably the sleep detection model extracts aplurality of features to improve the sensitivity and reliability of thesleep detection module. The inventors found that the mandibular activityrecorded by a gyroscope may provide for a particularly reliable awakestate detection. In particular, the following feature specific thresholdvalues were identified. The awake state may be determined when thestandard deviation of the gyroscope norm exceeds threshold of at least1.10 to at most 1.50, preferably 1.15 to 1.25, more preferably around1.20, such as 1.17. The awake state may be determined when the maximumvalue of the gyroscope norm exceeds threshold of at least 14.0 to atmost 15.0, preferably 14.1 to 14.9, or 14.2 to 14.8, more preferably14.3 to 14.5, or 14.3 to 14.4.

The sleep respiratory disturbances related metrics may include thehourly occurring rate and cumulated duration of respiratory effortsduring sleep. The analysis unit may be configured for reporting theinterpreted subject specific parameters. The reporting may includeproviding an output to a device, such as a computer or smartphone. Thereporting may also include providing a visual or textual report of thesubject specific parameters, for example in the form of a hypnogram.

In an embodiment the sleep detection module may be configured to changeone or more stimulation programs when a specific sleeping stage isdetected, specifically the recruitment program, the rehabilitationprogram and/or the retraining program. The session may be typicallyinitiated with the recruitment program and/or the rehabilitation programwhich will be applied during the initial sleeping stages (e.g. N1, N2).However, during deeper sleeping stages, specifically N3, the ventilationand the muscular pharyngeal walls (dedicated for the airway patency) aretypically more stable and hence require less electrical stimulation toproduce a beneficial response. Accordingly, the sleep detection modulemay be configured to switch the stimulator to the retraining program inorder to prevent possible muscle fatigue and/or conserving battery ofthe wearable device.

The wearable device may comprise a garment, specifically a wearablegarment, configured for holding at least part of the stimulator and/orsupporting the electrode. In an embodiment the wearable device maycomprise a collar, wherein said collar is configured for placementaround at least a portion of the subject's neck. In one embodiment thecollar may be rigid such that it can be placed onto the subject'sshoulders. An example of such an embodiment is shown in FIG. 2 . Inanother embodiment the collar may be flexible such that it can snaparound the subject's neck, advantageously providing a compressive forceon the subject's neck such that the collar is held in place around theneck during sleep. An example of such an embodiment is shown in FIG. 4 .In an embodiment the wearable device may comprise a headband, whereinsaid headband is configured for placement around at least a portion ofthe subject's head. The headband may similarly be rigid, flexible or acombination of both. An example of such an embodiment is shown in FIG. 5.

The garment may have a rigid body which is curved so that it can be fitaround the subject's body part, preferably the neck or head.Advantageously, the garment has a semi-circular or arched shape, whichmay improve the ergonomics of the design and prevent it from falling offduring sleep. The garment may be provided with a gap to allow for easierfitting around the neck.

Preferably, the garment body may be sufficiently stiff to protect theelectronics within, but flexible enough to ensure compliance with themovements of the subject. In an embodiment the garment has a rigidpolymer core covered by a silicon shell. Silicon is particularlywell-suited material to ensure pleasant skin contact. The components mayfor example be 3D-printed or moulded for larger production. The insidesection of the garment may be provided with a texture adapted to improvethe comfort for contact with the subject skin but also providesufficient surface friction to prevent displacement of the garment, dueto rotation of the body during sleep. In an embodiment the garment iscovered with a textile such as polyester or a polyamide to allow thematerial to breathe since it may be in skin contact for extended timeperiods.

In an embodiment, the garment may be configured to (lightly) press ontothe subject's body part, specifically the neck and/or head, to create acompressive force. This has the advantage that the garment can be moreeasily fixed in placed, for example during sleeping movements.Furthermore, the compressive force can be extended to the electrodessuch that the electrodes press onto the target stimulation zone.Compression of the electrode may improve skin contact, decrease skinresistance, and/or enable stimulation closer to the motor nerve. As aresult, this may increase the stimulation response and/or decreaseregional side effects or discomfort.

The electrodes may be electrically connected to the garment withconnective cables. In an embodiment the wearable device may be providedwith a flexible cable the length of which may be adjusted for easierplacement of the electrode onto the subject's skin and/or respond tomovements of the subject, such as rotation of the head or body. Thelength adjustment of the flexible cable may prevent the electrode fromdismounting from the subject skin. The garment may be provided with acable housing adapted for tensioning the cable and/or retracting excesscable, for instance by rolling it up into said housing. Optionally, alocking mechanism may be provided on the garment to secure the cable atdifferent lengths. Alternatively, the cable may be rigid, but this couldreduce sleep quality. The cable may be provided with electrical cablesto allow current to travel from the stimulator disposed in the garmentto the electrodes. An example of such an embodiment is shown in FIG. 2 .The electrodes may detachably attach to the cables to allow replacementof used or defective electrodes. In another embodiment the cables may beintegrated into a housing, which may be part of the garment. An exampleof such an embodiment is shown in FIG. 5 .

The garment may also be provided with a battery pack and optional plugto allow for electrical charging of said battery when the device is notin use, typically during daytime. Optionally, the garment may beprovided with user interface buttons, such as a power button.Additionally, a display may be provided that informs the subject aboutone or more actions, such as selected programs, information aboutbattery life or charging time, and so on.

The wearable device may be configured for connecting to an outputdevice, such as a smartphone, and transmitting data to said outputdevice. The output device may be provided with analytical software, suchas an application, which is configured to analyse the received data andoptionally determine various features from said data. The wearabledevice may comprise a storage means for storing stimulation data, suchas an overview of the stimulation parameters generated by thestimulator, which stored data may be exported to said output device foranalysis. In an embodiment wherein the wearable device is provided witha sensor, it may comprise a storage means for storing sensing data whichmay similarly be exported to said output device for analysis.

The output device may be configured to determine a subject specificprofile which may be used to, for example, adjust one or more one pulsespecific parameters of the pulsed electrical current or adjust one ormore one feature specific threshold value of the sleep detection module.Also, the subject specific profile may be used to provide user feedbackto promote the sleep quality improvements in the form of, for example,games or questionnaires investigating neurocognitive, quality of life,mood, and others biological/physiological measures.

Additionally, the output device may be configured to transmit thereceived data to a dedicated data analysis device, such as an externalserver, which is configured to determine from said received data morecomplicated features, for example, by means of machine learning model.

An aspect of the present disclosure relates to a method for decreasingthe respiratory effort of a subject during sleep, the method comprising:

-   -   selecting a portion of the subject's skin ranging from a left,        preferably masseter, pterygoid and/or temporalis, muscle motor        point to the left posterior angle of the mandible and        positioning a left electrode on the selected skin portion, and        selecting a portion of the subject's skin ranging from a right,        preferably masseter, pterygoid and/or temporalis, muscle motor        point to a right posterior angle of the mandible and positioning        a right electrode on the selected skin portion;    -   applying a transcutaneous electrical stimulation from the left        electrode to at least one left, preferably masseter, pterygoid        and/or temporalis, muscle and from the right electrode to at        least one right, preferably masseter, pterygoid and/or        temporalis, muscle;    -   wherein the applied electrical stimulation promotes the        contraction of said left and right stimulated, preferably        masseter, pterygoid and/or temporalis, muscles to controllably        elevate the subject's mandible such that the upper airway is        opened.

An aspect of the present disclosure relates to a method for decreasingthe respiratory effort of a subject being provided with a sensorconfigured for detecting the movement of the subject's mandible duringsleep, the method comprising:

-   -   outputting, by the sensor, a signal indicative of mandibular        activity;    -   receiving, by a signal processing unit, said signal indicative        of mandibular activity;    -   processing, by the signal processing unit, said signal        indicative of mandibular activity to determine mandibular        activity data;    -   actuating, by the signal processing unit, a stimulator by means        of a control signal, the control signal being produced by the        signal processing unit based on the determined mandibular        activity data;    -   generating, by the stimulator, an electrical stimulation        characterised by one more stimulation parameter suitable for        promoting the contraction of a, preferably masseter, pterygoid        and/or temporalis, muscle to controllably elevate the subject's        mandible such that the upper airway can be opened.

An aspect of the present disclosure relates to a method for decreasingthe respiratory effort of a subject being provided with a sensorconfigured for detecting the movement of the subject's mandible duringsleep, the method comprising:

-   -   outputting, by the sensor, a signal indicative of mandibular        activity;    -   receiving, by a signal processing unit, said signal indicative        of mandibular activity;    -   processing, by the signal processing unit, said signal        indicative of mandibular activity to determine respiratory        activity data;    -   optionally, determining, by the signal processing unit, the        occurrence of sleep disturbed breathing marked with increased        respiratory effort;    -   optionally, determining, by the signal processing unit, the        occurrence of a sleep respiratory disturbance;    -   actuating, by the signal processing unit, a stimulator by means        of a control signal, the control signal being produced by the        signal processing unit based on the determined respiratory        activity data, optionally based on the determined sleep        disturbed breathing and/or determined sleep respiratory        disturbance;    -   generating, by the stimulator, an electrical stimulation        characterised by one more stimulation parameter suitable for        promoting the contraction of a, preferably masseter, pterygoid        and/or temporalis, muscle to controllably elevate the subject's        mandible such that the upper airway can be opened.

An aspect of the present disclosure relates to a method for decreasingthe respiratory effort of a subject being provided with a sensorconfigured for detecting the movement of the subject's mandible duringsleep, the method comprising:

-   -   outputting, by the sensor, a signal indicative of mandibular        activity;    -   receiving, by a signal processing unit, said signal indicative        of mandibular activity;    -   processing, by the signal processing unit, said signal        indicative of mandibular activity to determine sleep activity        data;    -   optionally, determining, by the signal processing unit, a        sleeping state, said sleeping state including an awake state and        an asleep state;    -   optionally, determining, by the signal processing unit, a        sleeping stage, said sleeping stage including at least one stage        selected from a light (N1) sleeping stage, a light (N2) sleeping        stage, a deep (N3) sleeping stage N3 and/or REM sleeping;    -   actuating, by the signal processing unit, a stimulator by means        of a control signal, the control signal being produced by the        signal processing unit based on the determined sleep activity        data, optionally based on a determined sleeping state and/or        determined sleeping stage;    -   generating, by the stimulator, an electrical stimulation        characterised by one more stimulation parameter suitable for        promoting the contraction of a, preferably masseter, pterygoid        and/or temporalis, muscle to controllably elevate the subject's        mandible such that the upper airway can be opened.

In some preferred embodiments, the methods for decreasing therespiratory effort of a subject as described above may further comprise:

-   -   transmitting, by the stimulator, the generated electrical        stimulation to a left electrode positioned a selected portion of        the subject's skin ranging from a left, preferably masseter,        pterygoid and/or temporalis, muscle motor point to the left        posterior angle of the mandible;    -   transmitting, by the stimulator, the generated electrical        stimulation to a right electrode positioned on a selected        portion of the subject's skin ranging from a right, preferably        masseter, pterygoid and/or temporalis, muscle motor point to the        right posterior angle of the mandible;    -   applying, by the left electrode, a transcutaneous electrical        stimulation to at least one left, preferably masseter, pterygoid        and/or temporalis, muscle to promote contraction of said left,        preferably masseter, pterygoid and/or temporalis, muscle, and    -   applying, by the right electrode, a transcutaneous electrical        stimulation to at least one right, preferably masseter,        pterygoid and/or temporalis, muscle to promote contraction of        said right, preferably masseter, pterygoid and/or temporalis,        muscle; wherein the left and right stimulated, preferably        masseter, pterygoid and/or temporalis, muscles controllably        elevate the subject's mandible such that the upper airway is        opened.

An aspect of the present disclosure relates to a method for decreasingthe respiratory effort of a subject during said subject's sleep, themethod comprising:

-   -   selecting a portion of the subject's skin corresponding with the        position of at least one left target muscle including a left        masseter, a left pterygoid and/or a left temporalis muscle, and        mounting at least one left bipolar electrode comprising at least        two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the left target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the left target muscle fibre;    -   selecting a portion of the subject's skin corresponding with the        position of at least one right target muscle including a right        masseter, a right pterygoid and/or a right temporalis muscle,        and mounting at least one left bipolar electrode comprising at        least two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the right target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the right target muscle fibre;    -   applying a biphasic transcutaneous electrical stimulation        between the two electrically conductive elements of the left and        right bipolar electrodes, which electrical stimulation promotes        the contraction of the target muscles to controllably elevate        the subject's mandible so that the respiratory effort can be        decreased; wherein said electrical stimulation is generated        according to a duty cycle that has a stimulation period of 1 sec        to 20 sec and/or a rest period of 1 sec to 20 sec.

An aspect of the present disclosure relates to a method for decreasingthe respiratory effort of a subject during said subject's sleep, themethod comprising:

-   -   selecting a portion of the subject's skin corresponding with the        position of at least one left target muscle including a left        masseter, a left pterygoid and/or a left temporalis muscle, and        mounting at least one left bipolar electrode comprising at least        two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the left target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the left target muscle fibre;    -   selecting a portion of the subject's skin corresponding with the        position of at least one right target muscle including a right        masseter, a right pterygoid and/or a right temporalis muscle,        and mounting at least one left bipolar electrode comprising at        least two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the right target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the right target muscle fibre;    -   applying a biphasic transcutaneous electrical stimulation        between the two electrically conductive elements of the left and        right bipolar electrodes, which electrical stimulation promotes        the contraction of the target muscles to controllably elevate        the subject's mandible so that the respiratory effort can be        decreased; wherein said electrical stimulation is generated        according to a duty cycle that has a stimulation period of 1 sec        to 20 sec and/or a rest period of 1 sec to 20 sec.

An aspect of the present disclosure relates to a method for recruitingof a target muscle to decrease the respiratory effort of a subjectduring said subject's sleep, the method comprising:

-   -   selecting a portion of the subject's skin corresponding with the        position of at least one left target muscle including a left        masseter, a left pterygoid and/or a left temporalis muscle, and        mounting at least one left bipolar electrode comprising at least        two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the left target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the left target muscle fibre;    -   selecting a portion of the subject's skin corresponding with the        position of at least one right target muscle including a right        masseter, a right pterygoid and/or a right temporalis muscle,        and mounting at least one left bipolar electrode comprising at        least two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the right target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the right target muscle fibre;    -   applying a biphasic transcutaneous electrical stimulation        between the two electrically conductive elements of the left and        right bipolar electrodes, which electrical stimulation promotes        the contraction of the target muscles to controllably elevate        the subject's mandible so that the respiratory effort can be        decreased;    -   wherein said electrical stimulation is generated according to        the following stimulation parameters: a current intensity        between 5 mA to 10 mA, preferably 6 mA to 10 mA; a frequency        between 15 Hz to 50 Hz, preferably 25 Hz to 45 Hz, more        preferably 30 Hz to 40 Hz; a pulse width between 50 μs to 300        μs, preferably 225 μs to 275 μs, more preferably 200 μs to 250        μs; and, a duty cycle with a stimulation period of 1 sec to 20        sec and/or a rest period of 1 sec to 20 sec.

An aspect of the present disclosure relates to a method forrehabilitating the muscle function of a target muscle to decrease therespiratory effort of a subject during said subject's sleep, the methodcomprising:

-   -   selecting a portion of the subject's skin corresponding with the        position of at least one left target muscle including a left        masseter, a left pterygoid and/or a left temporalis muscle, and        mounting at least one left bipolar electrode comprising at least        two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the left target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the left target muscle fibre;    -   selecting a portion of the subject's skin corresponding with the        position of at least one right target muscle including a right        masseter, a right pterygoid and/or a right temporalis muscle,        and mounting at least one left bipolar electrode comprising at        least two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the right target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the right target muscle fibre;    -   applying a biphasic transcutaneous electrical stimulation        between the two electrically conductive elements of the left and        right bipolar electrodes, which electrical stimulation promotes        the contraction of the target muscles to controllably elevate        the subject's mandible so that the respiratory effort can be        decreased;    -   wherein said electrical stimulation is generated according to        the following stimulation parameters: a current intensity        between 1 mA to 4 mA, preferably 2 mA to 4 mA; a frequency        between 15 Hz to 50 Hz, preferably 20 Hz to 45 Hz, more        preferably 30 Hz to 40 Hz; a pulse width between 50 μs to 300        μs, preferably 225 μs to 275 μs, more preferably 200 μs to 250        μs; and, a duty cycle with a stimulation period of 1 sec to 20        sec and/or a rest period of 1 sec to 20 sec.

An aspect of the present disclosure relates to a method for retrainingof a neuromuscular related circuit to decrease the respiratory effort ofa subject during said subject's sleep, the method comprising:

-   -   selecting a portion of the subject's skin corresponding with the        position of at least one left target muscle including a left        masseter, a left pterygoid and/or a left temporalis muscle, and        mounting at least one left bipolar electrode comprising at least        two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the left target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the left target muscle fibre;    -   selecting a portion of the subject's skin corresponding with the        position of at least one right target muscle including a right        masseter, a right pterygoid and/or a right temporalis muscle,        and mounting at least one left bipolar electrode comprising at        least two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the right target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the right target muscle fibre;    -   applying a biphasic transcutaneous electrical stimulation        between the two electrically conductive elements of the left and        right bipolar electrodes, which electrical stimulation promotes        the contraction of the target muscles to controllably elevate        the subject's mandible so that the respiratory effort can be        decreased; wherein said electrical stimulation is generated        according to the following stimulation parameters: a current        intensity between 1 mA to 4 mA, between 2 mA to 4 mA; a        frequency between 50 Hz to 150 Hz, preferably between 70 Hz to        130 Hz, even more preferably 90 Hz to 110 Hz; a pulse width        between 500 μs to 1000 μs, preferably between 600 s to 900 μs,        more preferably 700 μs to 800 μs; and, a duty cycle with a        stimulation period of 1 sec to 20 sec and/or a rest period of 1        sec to 20 sec.

An aspect of the present disclosure relates to treating the snoring of asubject. The treating of snoring may be regarded as a reduction insnoring intensity, for example half the snoring intensity, or thealtogether prevention of snoring, for example a full reduction insnoring intensity. The prevention of snoring may thus also be consideredas a reduction in snoring. In some preferred embodiments, the methodsfor decreasing the respiratory effort of a subject as described abovemay be a method for treating the snoring of a subject. The inventorsfound that applying a transcutaneous electrical stimulation topreferably the masseter, pterygoid and/or temporalis muscles tocontrollably elevate t preferably the he subject's mandible such thatthe upper airway is opened may prevent the subject from snoring or atthe very least reduce the subject's snoring intensity.

In an embodiment the method for treating snoring may comprise:

-   -   selecting a portion of the subject's skin ranging from a left,        preferably masseter, pterygoid and/or temporalis, muscle motor        point to a left posterior angle of the mandible and positioning        a left electrode on said selected skin portion, and selecting a        portion of the subject's skin ranging from a right, preferably        masseter, pterygoid and/or temporalis, muscle motor point to a        right posterior angle of the mandible and positioning a right        electrode on said selected skin portion;    -   applying a transcutaneous electrical stimulation from the left        electrode to at least one left, preferably masseter, pterygoid        and/or temporalis, muscle and from the right electrode to at        least one right, preferably masseter, pterygoid and/or        temporalis, muscle;    -   wherein the applied electrical stimulation promotes the        contraction of said left and right stimulated, preferably        masseter, pterygoid and/or temporalis, muscles to controllably        elevate the subject's mandible such that the upper airway is        opened, and snoring is reduced and/or prevented.

The subject may be provided with a sensor configured for detecting thesnoring of the subject. The snoring signal may be derived frommandibular activity data, as discussed above, or by means of a dedicatedsnoring sensor, such as a microphone provided on or near the subject.

In an embodiment the method for treating snoring may comprise:

-   -   receiving, by a signal processing unit, said signal indicative        of snoring;    -   processing, by the signal processing unit, said signal        indicative of snoring;    -   actuating, by the signal processing unit, a stimulator by means        of a control signal, the control signal being produced by the        signal processing unit based on the signal indicative of        snoring;    -   generating, by the stimulator, an electrical stimulation        characterised by one more stimulation parameter suitable for        promoting the contraction of a, preferably masseter, pterygoid        and/or temporalis, muscle to controllably elevate the subject's        mandible such that the upper airway can be opened and snoring is        reduced or prevented.

An aspect of the present disclosure relates to a method for treatingsnoring of a subject during said subject's sleep, the method comprising:

-   -   selecting a portion of the subject's skin corresponding with the        position of at least one left target muscle including a left        masseter, a left pterygoid and/or a left temporalis muscle, and        mounting at least one left bipolar electrode comprising at least        two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the left target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the left target muscle fibre;    -   selecting a portion of the subject's skin corresponding with the        position of at least one right target muscle including a right        masseter, a right pterygoid and/or a right temporalis muscle,        and mounting at least one left bipolar electrode comprising at        least two electrically conductive elements on said selected skin        portion, wherein a first electrically conductive element is        mounted on the right target muscle's motor point and a second        electrically conductive element is mounted along the direction        of the right target muscle fibre;    -   applying a biphasic transcutaneous electrical stimulation        between the two electrically conductive elements of the left and        right bipolar electrodes, which electrical stimulation promotes        the contraction of the target muscles to controllably elevate        the subject's mandible so that the snoring is reduced or        prevented; wherein said electrical stimulation is generated        according to a duty cycle that has a stimulation period of 1 sec        to 20 sec and/or a rest period of 1 sec to 20 sec.

An aspect of the present disclosure relates to a method for assisting inthe characterization of respiratory effort of a subject being providedwith a sensor configured for detecting the movement of the subject'smandible during sleep, the method comprising the steps:

-   -   outputting, by the sensor, a signal indicative of mandibular        activity;    -   receiving, by a data analysis unit, said signal indicative of        mandibular activity;    -   storing, by means of a memory unit comprised in the data        analysis unit, N mandibular activity classes, N being an integer        larger than one; wherein at least one of the N mandibular        activity classes is indicative of a sleep disturbed breathing;    -   wherein each j^(th) (1≤j≤N) mandible movement class consists of        a j^(th) set of rotational values, each j^(th) set of rotational        values being indicative of at least one rate of mandibular        rotations;    -   associated with the j^(th) class;    -   sampling, by means of a sampling element comprised in the data        analysis unit, the mandibular activity data during a sampling        period, thereby obtaining sampled mandibular activity data;    -   deriving, by means of the data analysis unit, a plurality of        mandibular activity values from the sampled mandibular activity        data; and,    -   matching, by means of the data analysis unit, the mandibular        activity values to the N mandibular activity classes of which at        least one of the N mandibular activity class is indicative of a        sleep disturbed breathing.

In some embodiments at least one of the N mandibular activity classes isindicative of a sleep disturbed breathing marked with increasedrespiratory effort.

In some embodiments at least one of the N mandibular activity classes isindicative of a sleep respiratory disturbance.

An aspect of the present disclosure relates to a method for assisting inthe characterization of respiratory effort of a subject being providedwith a sensor comprising a gyroscope configured for detecting themovement of the subject's mandible during sleep, the method comprisingthe steps:

-   -   outputting, by the sensor preferably the gyroscope, a signal        indicative of mandibular activity;    -   receiving, by a data analysis unit, said signal indicative of        mandibular activity;    -   storing, by means of a memory unit comprised in the data        analysis unit, N mandibular activity classes, N being an integer        larger than one; wherein at least one of the N mandibular        activity classes is indicative of a sleep disturbed breathing;    -   wherein each j^(th) (1≤j≤N) mandible movement class consists of        a j^(th) set of rotational values, each j^(th) set of rotational        values being indicative of at least one rate of mandibular        rotations;    -   associated with the j^(th) class;    -   sampling, by means of a sampling element comprised in the data        analysis unit, the mandibular activity data during a sampling        period, thereby obtaining sampled mandibular activity data;    -   deriving, by means of the data analysis unit, a plurality of        mandibular activity values from the sampled mandibular activity        data; and,    -   matching, by means of the data analysis unit, the mandibular        activity values to the N mandibular activity classes of which at        least one of the N mandibular activity class is indicative of a        sleep disturbed breathing.

EXAMPLES

To better illustrate the properties, advantages and features of thepresent disclosure some preferred embodiments are disclosed as exampleswith reference to the enclosed figures. However, the scope of thepresent disclosure is by no means limited to the illustrative examplesdescribed below.

Example 1: Wearable Device Design

With reference to FIG. 2 , a wearable (10) according to an embodiment ofthe present disclosure is shown. The wearable (10) comprises at leastone left electrode (100) and at least one right electrode (not shown).Each electrode (100) is connected to a garment (200), specifically acollar by means of at least one connective cable (150). The collar mayhouse the stimulator and any ancillary devices, such as a power sourcee.g. battery pack configured for powering the stimulator, and acontroller for controlling the stimulation generated by the powersource. The connective cable (150) then provides for an electricalconnection between the electrodes (100) and the stimulator.

With reference to FIG. 3 , a wearable (10) according to anotherembodiment of the present disclosure is shown. The wearable (10) alsocomprises at least one left electrode (100) and at least one rightelectrode (not shown), which are connected to a garment (200),specifically a collar, by means of a rigid housing extending sidewaysfrom said collar. The connective housing allows the integration of oneor more cables within. The collar may be configured to (lightly) pressonto the subject's neck such that it remains fixed in place. Moreover,the collar can be configured to create a compression on the electrode,which may increase the stimulation response and/or decrease discomfort.

With reference to FIG. 5 , a wearable (10) according to anotherembodiment of the present disclosure is shown. The wearable (10) alsocomprises at least one left electrode (100) and at least one rightelectrode (not shown), which are connected to a garment (200),specifically a headband, by means of a rigid housing extending downwardsfrom said headband. The collar may be configured to (lightly) press ontothe subject's head such that it remains fixed in place.

Example 2: Stimulation Zone

To achieve an optimal stimulation response and/or reduced stimulationdiscomfort, each electrode (100) of the wearable may be positioned intoelectrical contact with a selected portion of the subject's skin. Thepreferred skin portion is illustrated in FIG. 1 and ranges from asubject's masseter muscle motor point to a posterior angle of thesubject's mandible.

In order to locate the areas of interest over the superficial masseter(SM) muscle, one straight line can be determined from easily palpableanatomical landmarks. With reference to FIG. 7 these landmarks can beidentified. Specifically, FIG. 7A shows the lateral view of a skullswith the reference lines, TL_(V), TL_(H) and ML. The small thick linerepresents an intersection about 40% length of the masseter muscle line(ML) from Gonion (Go). FIG. 7B further shows a lateral view of deepfacial planes, evidencing the anterior temporalis (AT) and superficialmasseter (SM) muscles and their relationship with anatomical landmarksand reference lines adopted. With further reference to FIG. 8 the samelandmarks are drawn on the face of a human subject. Specifically, FIG.8A shows the lateral view of a subject's head with the same referencelines, TL_(V), TL_(H) and ML. Further, FIG. 88 shows the placement ofelectrodes over the AT and SM muscles. In a clinical setting, optimalplacement of electrodes over the superficial masseter (SM) muscle,gonion-located at the angle of the mandible (gonial angle)—and the bodyof zygomatic bone can be performed through palpation to identifyanatomical reference landmarks. The superficial masseter muscle line isdrawn from these reference landmarks, joining gonion, spotted on thesoft tissue, to the mid-point between the lower posterior border of thezygomatic bone and the zygomatic arch, both also identified bypalpation.

The line is adjusted to fibres direction of superficial masseter muscle,which is congruent with its origin and insertion. The superficialmasseter muscle is covered by a tendinous layer that extends from thezygomatic bone to ⅓ to ½ of its length. It is not recommended to placeelectrodes over tendinous areas, so a reference point is identified at40% of the length of line from the gonion or gonial angle (Go). Theelectrodes are placed along this reference line, with their location ofplacement on the mark corresponding to 40% of the line.

After setting out all the reference points and lines, the subject may beasked to clench the teeth so as to confirm whether the suggestedanatomical landmarks needed any adjustments.

The surface electrodes are advantageously placed along the musclefibres, over the most prominent region at the moment of musclecontraction to improve stimulation response. While palpating the muscleduring contraction, it can be possible to verify electrodes positioningto perform any need of correction.

In a home setting, optimal placement of electrodes onto the preferredstimulation zone (S) can be achieved by following the steps of an easieruser guide. With reference to FIG. 9 , this placement guide will bediscussed as a method comprising the following steps:

-   -   FIG. 9 (I) identifying the gonial angle (Go); preferably at the        outer corner of the mandible;    -   FIG. 9 (II) identifying the zygomatic arch (Za); preferably at        the outer corner of the eye;    -   FIG. 9 (III) identifying a muscle extending from Go towards Za;        preferably by gritting the teeth to contract this muscle;    -   FIG. 9 (iv) identifying a target stimulation zone (S) ranging        from the Go towards the centre of the identified muscle        determined along the direction of the muscle fibres;    -   FIG. 9 (v) placing of at least one electrode over the        stimulation zone (S), preferably a bipolar electrode wherein one        electrode is placed adjacent to the gonial angle (Go) and the        other electrode is placed adjacent to the centre of the        identified muscle determined along the direction of the muscle        fibres. An example of a bipolar electrode is shown in FIG. 9 .

It is understood that variations on the above-discussed method may bedeveloped to identify the same target stimulation by identifyingdifferent anatomical landmarks. Nonetheless, this method presents aparticularly easy to follow guide for at-home and/or clinicalapplications of the wearable device and accordingly forms a preferredembodiment of the present disclosure.

Example 3: Stimulation Effects

In order to assess the viability of an electrical stimulation on thetarget stimulation zone (as defined in Example 2) a number of researchprotocols has been set up on different subjects with various stimulationparameters. The recorded data is discussed below.

Short-Term Effect

The efficacy of a transcutaneous electrical stimulation with a highcurrent intensity at a low frequency with narrow pulse width wasverified to determine if recruiting the muscular fibres may provide fora direct and acute response to prevent the occurrence of a sleepdisturbance.

One subject was selected for overnight stimulation. The subject was 53years old female volunteer with BMI of 26.2 kg/m². The sleeping stagewas monitored using laboratory polysomnography. Airflow was measured bymeans of a pressure transducer and thermistor.

The electrical stimulation was applied to the masseter muscles throughtwo electrodes placed above the motor point of the muscles and on theposterior angle of the mandible, respectively. The electrode consistedof a bipolar surface electrode with an inter electrode distance of 20mm, 14 mm diameter for conductive area, adhesive wet gel and foambacking backed. The stimulation consisted of a biphasic pulse current ata frequency of 40 Hz with a current intensity of 7 mA, a pulse width of250 μs and activation periods of five seconds of stimulation and fiveseconds of rest.

The results indicated that the electrical stimulation caused a directmuscle response that results in an elevation of the mandible sufficientto maintain good air flow throughout the any sleeping stage,specifically the N2 stage. Accordingly, the occurrence of sleepdisturbances could be prevented by means of the applied electricalstimulation.

Long-Term Effect

Two subjects were selected for overnight stimulation. The first subjectwas 61 years old male volunteer with BMI of 24.8 kg/m. The secondsubject was 38 years old male volunteer with BMI of 29.8 kg/m². Therespiratory event index (OAHI—obstructive apnea hypopnea index) and thesleep fragmentation index (ArI—arousal index) were measured duringlaboratory polysomnography for both patients at baseline (week 0), afterone week of stimulation (week 1) and one week after the stimulation wasswitched off (week 2).

The electrical stimulation was applied to the masseter muscles throughtwo electrodes placed above the motor point of the muscles and on theposterior angle of the mandible, respectively. The electrode consistedof a bipolar surface electrode with an inter electrode distance of 20mm, 14 mm diameter for conductive area, adhesive wet gel and foambacking backed. The stimulation consisted of a biphasic pulse current ata frequency of 40 Hz, with a pulse width of 250 μs, activation periodsof five seconds of stimulation and five seconds of rest, and a currentwith a current intensity of 6 and 8 mA, respectively. The results of thefirst subject are presented in the table below:

Condition OAHI (events/h) Arl (events/h) Week 0 31.7 39.8 Week 1 12.623.2 Week 2 22.4 32.1

The data of the first subject demonstrate that after one week (week 1)of stimulation a decrease of 60.3% for OHAI can be observed. After thefollowing week (week 2) without stimulation still a decrease of 29.3%for OAHI persists compared to the baseline (week 0).

The results of the second subject are presented in the table below:

Condition OAHI (events/h) Arl (events/h) Week 0 15.6 38.3 Week 1  3.423.6 Week 2 11.4 30.2

The data of the second subject demonstrate that after one week (week 1)of stimulation a decrease of 78.2% for OHAI can be observed. After thefollowing week (week 2) without stimulation still a decrease of 26.9%for OAHI persists compared to the baseline (week 0).

The results indicated that the electrical stimulation caused aretraining of the muscles with a delayed response effect that improvedthe beneficial effects of the stimulation across successive stimulationsessions and provided persisting effects even after the stimulation wasterminated.

Respirator Events

Six subjects were selected for overnight stimulation. The reduction ofthe respiratory event index (OAHI—obstructive apnea hypopnea index) andof the sleep fragmentation index (ArI—arousal index) were measuredduring laboratory polysomnography after two weeks of stimulationcompared to baseline values.

Electrical stimulation was applied to the masseter muscles through twoelectrodes placed above the motor point of the muscles and on theposterior angle of the mandible, respectively. Bipolar surface electrodewith inter electrode distance of 20 mm, 14 mm diameter for conductivearea, adhesive wet gel, foam backing backed was mounted on the face of avolunteer individual with normal occlusion, awake.

The participants were allocated to one of two stimulation protocols,varying the rest-duration period of the night stimulation (protocol A: 5sec ON/5 sec OFF without pause throughout the night; protocol B: 5 secON/5 sec OFF with 1 minute pause every minute of stimulation throughoutthe night). The results are presented below in Table 1.

TABLE 1 electrical stimulation parameters and stimulation response MeanMean Mean current OAHI* ArI** Stimulation age BMI intensity after(events/ (events/ parameters (years) Gender (kg/m²) 2 weeks (mA) h) h)40 Hz 250 μs 5 s 43.3 1 female + 27.6 5.6 −66% −32% on 5 s off 2 males40 Hz 250 μs 5 s 48.3 1 female + 27.9 5.5 −45% −21% on 5 s off - 2 males1 min rest for every 1 min stim *Obstructive apnea hypopnea (OAHI) indexindicates the mean reduction of the respiratory events **arousal index(ArI) indicates the mean reduction of the sleep fragmentation

The results presented above in Table 1 indicate that transcutaneouselectrical stimulation applied to the masseter muscles are effective inreducing the occurrence of respiratory events and arousal index by asubstantial amount. The reduction of the occurrence of respiratoryevents and arousal index was more important for the group without the 1minute pause every minute of stimulation.

Example 4: Stimulation Parameters

The implementation of an electrical stimulation on a target stimulationzone was assessed on different subjects using various stimulationparameters and electrode set-ups. The results are discussed throughoutpresent Example 4.

Electrode Type

Bipolar surface electrode was mounted on the face of a volunteerindividual with normal occlusion, awake. The electrical stimulation wasapplied as a biphasic pulse current at a frequency of 40 Hz, with awidth of 250 μs and activation periods of five seconds of stimulationand five seconds of rest. The closing force of the jaw was evaluatedusing a pressure sensor implemented in a bite (FUTEK Advanced SensorTechnology, Inc., Irvine, Calif., USA). Electrodes are positioned on themasseter and the temporalis muscles according to the preferred methoddescribed in Example 2. The results are presented below in Table 2.

TABLE 2 electrical stimulation parameters and stimulation responseReported Inter Maximum comfort Closing Type of Diameter of electrodetolerated (visual force of Electrode type gel** and conductive distancecurrent scale the jaw and position* backing*** area (mm) (mm) (mA) 0 to10) (Nm) Type 1a (SM) awg, fbb 14 20 10 9 42 Type 1b (SM) awg, fbb 14 305.5 4 25 Type 2 (SM) awg, fbb 25 20 6 6 30 Type 3 (SM) awg, tb 14 30 5.54 25 Type 4 (SM) awf, fbb 14 20 6.5 6 30 Type 1a (SM + awg, fbb 14 20 10mA SM 9 45 AT) 2 mA AT Type 1b (SM + awg, fbb 14 30 5.5 mA SM 4 27 AT) 4mA AT Type 2 (SM + awg, fbb 25 20 6 mA SM 6 32 AT) 1.5 mA AT Type 3(SM + awg, tb 14 30 5.5 mA SM 4 27 AT) 4 mA AT Type 4 (SM + awf, fbb 1420 6.5 mA SM 6 32 AT) 2.5 mA AT *Anterior temporalis (AT) and/orsuperficial masseter (SM) muscles **Adhesive wet gel (awg); Adhesive wetfoam (awf) **Foam backing backed (fbb); Tissue backed (tb)

The results presented above in Table 2 indicate that a bipolar surfaceelectrode mounted on the masseter muscles with an inter electrodedistance of 20 mm, 14 mm diameter for conductive area, adhesive wet geland foam backing backed provides for the highest reported comfort level(9 out of 10 on a visual scale) while also stimulates a strong closingforce of the jaw (42 Nm). Similar results are obtained for the samebipolar surface electrode mounted on the masseter and temporalismuscles.

Electrode Positioning

Bipolar surface electrode with inter electrode distance of 20 mm, 14 mmdiameter for conductive area, adhesive wet gel, foam backing backed wasmounted on the face of a volunteer individual with normal occlusion,awake. The electrical stimulation was applied as a biphasic pulsecurrent at a frequency of 40 Hz, with a width of 250 μs and activationperiods of five seconds of stimulation and five seconds of rest. Theclosing force of the jaw was evaluated using a pressure sensorimplemented in a bite (FUTEK Advanced Sensor Technology, Inc., Irvine,Calif., USA). The results are presented below in Table 3.

TABLE 3 electrical stimulation parameters and stimulation responseReported Maximum comfort Closing Description of the tolerated (visualforce of position of the current scale the jaw Electrode position*electrodes (mA) 0 to 10) (Nm) Position 1 (SM) Positioned on the SM as 109 42 described in Example 2 Position 2 (SM) 90° rotation of theelectrodes  8 4 24 Position 3 (SM) Upper part of the SM  5 3  4 Position1 (AT) Positioned on the AT as  2 4  4 described in Example 2 Position 2(AT) 90° rotation of the electrodes  2 3  2 Position 3 (AT) Lower partof the  1.5 2  2 temporalis −30° rotation Position 1 (SM + AT)Positioned on the SM and 10 mA SM 9 45 the AT as described in Example 2 2 mA AT Position 2 (SM + AT) 90° rotation of the electrodes  8 mA SM 425  2 mA AT *Anterior temporalis (AT) and/or superficial masseter (SM)muscles

he results presented above in Table 3 indicate that a bipolar surfaceelectrode mounted on the target stimulation zone on the masseter musclesand optionally on the temporalis muscles according to the method asdescribed in Example 2 provides for the highest reported comfort level(9 out of 10 on a visual scale) while also stimulate a strong closingforce of the jaw (42 Nm).

Stimulation Parameters

Bipolar surface electrode with inter electrode distance of 20 mm, 14 mmdiameter for conductive area, adhesive wet gel, foam backing backed wasmounted on the face of a volunteer individual with normal occlusion,awake. The bipolar surface electrode mounted on the target stimulationzone on the masseter muscles according to the method as described inExample 2. The electrical stimulation was applied as a biphasic pulsecurrent with activation periods of five seconds of stimulation and fiveseconds of rest. The closing force of the jaw was evaluated using apressure sensor implemented in a bite (FUTEK Advanced Sensor Technology,Inc., Irvine, Calif., USA). Electrodes are positioned on the masseterand the temporalis muscles according to the preferred method describedin Example 2. The results are presented below in Table 4.

TABLE 4 electrical stimulation parameters and stimulation responseMaximum Reported Closing force Stimulation tolerated comfort (visual ofthe parameters current (mA) scale 0 to 10) jaw (Nm) 40 Hz 250 μs 10 9 4260 Hz 250 μs  6.5 5 28 20 Hz 250 μs 12.5 6 33 40 Hz 150 μs 14.5 7 40 40Hz 350 μs  8.5 6 31

The results presented above in Table 4 indicate that an electricalstimulation with a frequency of 40 Hz and a pulse width of 250 μsprovide for the highest reported comfort level (9 out of 10 on a visualscale) while also stimulate a strong closing force of the jaw (42 Nm).

It is understood that the embodiments presented in Tables 2-4 of presentExample 3 form preferred embodiments of the wearable device of thepresent disclosure.

Example 5: Sensing Unit Feedback

The wearable (10) of the present disclosure may be provided with asensing unit configured for recording of mandibular movement of thesubject's mandible. For example, the sensing unit may comprise agyroscope and/or accelerometer mounted on at least one electrode (100),preferably both a gyroscope and/or accelerometer mounted on at least oneelectrode (100). The mandibular movement may refer to any changes in theposition of the subject's mandible or any rotations or displacements ofthe subject's mandible. The mandibular movement may be recorded bysensing unit as mandibular activity data.

Additionally, the sensing unit may also be configured to record datarelated to the subject's respiration activity or sleeping activity. Therespiration activity data may refer to any data related to the subject'srespiration, such as breathing rate or intensity. respiration activitydata may also be derived from the mandibular activity data or combinedwith the mandibular activity data. Similarly, the sleeping activity datamay refer to any data related to the subject's sleeping, such as sleeprelated movements. sleeping activity data may also be derived from themandibular activity data or combined with the mandibular activity data.respiration activity data may also be combined with the sleepingactivity data.

The mandibular activity data, respiration activity data and sleepingactivity data may be analysed to provide a feedback loop to thestimulator to improve the stimulation efficacy and reduce the occurrenceof drawbacks. An exemplary working principle of feedback loop accordingto a preferred embodiment of the present disclosure is presented in FIG.11 . Below some exemplary embodiments are presented which were found tobe particularly well-suited for the present invention. It is, however,understood that the various embodiments described in the presentdisclosure may be combined in any suitable manner, as would be apparentto a person skilled in the art from this disclosure.

-   -   In a particular embodiment the mandibular activity data may be        analysed to determine a stimulation response, which may include        the elevation and stabilisation of the subject's mandible and        instruct the stimulator to adjust one or more stimulation        parameters to control the elevation and stabilisation of the        subject's mandible. It may also be used to determine the        occurrence of muscle fatigue.    -   In a particular embodiment the respiration activity data may be        analysed to determine sleep disturbed breathing marked with        increased respiratory effort and instruct the stimulator to        adjust one or more stimulation parameters to decrease the        respiratory effort.    -   In a particular embodiment the respiration activity data may be        analysed to determine a sleep respiratory disturbance and        instruct the stimulator to adjust one or more stimulation        parameters to reduce the intensity of the sleep respiratory        disturbance or prevent the occurrence of a further sleep        respiratory disturbance.    -   In a particular embodiment the sleep activity data may be        analysed to determine sleeping states, such as an awake state        and an asleep state. The stimulator may be instructed to        initiate the electrical stimulation when the subject falls        asleep and terminate the electrical stimulation when the subject        awakes.    -   In a particular embodiment the sleep activity data may be        analysed to determine sleeping stages, which may include a light        sleeping (N1) stage, a light sleeping (N2) stage, a REM stage,        and/or a deep sleeping (N3) stage. The stimulator may be        instructed to initiate the electrical stimulation when the        subject enters the light sleeping (N1) stage, the light sleeping        (N2) stage and/or the REM stage and terminate the electrical        stimulation when the subject enters the deep sleeping (N3)        stage.

Example 6: Sleeping Stage Detection

In order to assess the viability of a sleeping stage determinationmodule a research protocol has been set up according to the followingparameters. Mandibular movement data (MM) was collected from 30participants, each participant was provided with a “chin sensor” and a“cheek sensor”. The check sensor was located at the preferred targetstimulation zone discussed in Example 2 of the present disclosure, i.e.,at the same location as the electrode. The research aimed to identifydifferences in sleep analysis quality based on MM data obtained from thechin sensor and the cheek sensor. The feasibility of implementing anaccurate sleeping stage determination module in the wearable device asdisclosed herein can be assessed based on these results.

Primary Objectives

-   -   Detection of sleep/wake states from cheek-derived MM with enough        performances.    -   Determination of sleep/wake detection rules for cheek MM data        that can efficiently approximate sleep/wake algorithm analysis        from the chin sensor.

Hypothesis

-   -   Total sleeping time (TST) differences between the cheek and the        chin MM sensor are no greater than what is expected from        interscorer variability (^(˜)85%).    -   Application of simple detection rules to cheek-derived MM        features should allow for detection of sleep and wake states        with >75% accuracy.

Methods

Prospective study of consenting adult patients referred for a singleovernight in-laboratory polysomnography (PSG), complemented bysimultaneous mandibular movements (MM) recording using two devices. Datasamples from 30 participants were obtained by enrolling subjects fromroutine practice in a sleep laboratory during a 3-month period.

The study apparatus consisted of 2 coin-sized devices attached by thesleep technician on the chin (between the inferior labial sulcus and thepogonion) and the cheek (on the surface of the masseter muscle) of theparticipants, respectively.

Results and Processing

The MM data of a single selected participant recorded with the chinsensor is shown in FIG. 12 and the corresponding MM data recorded withthe cheek sensor is shown in FIG. 13 . The figures indicate theoccurrence of sleeping states and obstructive respiratory events withrespect to the time of night (x-axis). The MM data is divided into 3parts based on the awake and asleep states as recorded by the sensors.The occurrence of obstructive respiratory events is indicated on the MMdata—differences may be attributed to algorithm calibration.

The collected MM data were automatically transferred to a cloud-basedinfrastructure at the end of the night, and data analysis was conductedwith a dedicated machine-learning algorithm. The algorithm analysed thetime series data from the cheek device in order to precisely identifysequential 30 seconds epochs of MM raw signals as wake or sleep, basedon relevant and non-redundant features. Each 30 seconds epoch wassummarized by 11 features extracted from the gyroscope norm:

-   -   a. Standard deviation    -   b. Minimum values and differences in minimum values in adjacent        30 sec windows    -   c. Maximum values and differences in maximum values in adjacent        30 sec windows    -   d. Median value and differences in median values in adjacent 30        sec windows    -   e. 1st quartile and differences in Q1 values in adjacent 30 sec        windows    -   f. 3rd quartile and differences in Q3 values in adjacent 30 sec        windows

For the purposes of this study gyroscope data was selected as it is moresensitive to sleep/wake variations; accelerometer data was notconsidered. Normalized histograms were produced to investigate thedistribution of these features in both sleep and wake.

Algorithm-derived sleep/wake labels were extracted from the chin sensor.The relevant features were extracted from the corresponding MM rawsignal sequences and were used as input data for the algorithm todetermine whether they pertained to wake or sleep states.

The cheek-derived MM features were then used to best classify thechin-derived sleep/wake labels. This investigation led to the selectionof 2 features with the most discriminative power: standard deviation(SD) and maximum value (MAX) of the MM data recorded by the gyroscope.The processed data is shown with reference to FIG. 14-17 . Specifically,FIG. 14 shows the frequency distribution of SD values for both sleep(light) and wake (dark) states. FIG. 15 shows thesensitivity/specificity across all possible SD values for detection ofsleep and wake state. FIG. 16 shows the frequency distribution of MAXvalues for both sleep (light) and wake (dark) states. Finally, FIG. 17shows the sensitivity/specificity across all possible MAX values fordetection of sleep and wake state.

Data Analysis

The data analysis algorithm can be configured for automated detection ofsleep and wake states by considering the sensitivity/specificity valuesand the processed cheek-derived MM features. Additionally, the cut-offsfor optimizing the detection of sleep/wake states can be kept generic(i.e., cut-offs are kept the same across all individuals—FIG. 18 ) orpersonalised (i.e., cut-offs are adjusted to an individual's sleepingprofile—FIG. 22 ). The cut-off values will have an impact on the totalsleep time (TST), i.e., the amount of time that the individual spendsactually sleeping during a planned sleep episode. The followingparameters can be determined by comparing the chin TST data values tothe cheek TST data, cheek SD and cheek MAX values: Diff_TST refers tothe % difference between “Chin—data” and “Cheek—data”; Diff_TST1 refersto the % difference between “Chin—data” and “Cheek—SD”; and Diff_TST2refers to the % difference between “Chin—data” and “Cheek—MAX”. Thisdata analysis algorithm may be implemented as a configuration of thesleep detection module of the present disclosure.

Three different implementations can be considered for the data analysisalgorithm:

-   -   Wake state detection: The data analysis algorithm can be        configured for optimal detection of the wake state by        constraining the sensitivity to 0.9 and maximizing specificity.        This configuration may for example maximize patients' comfort by        preventing stimulation during the wake state and/or light sleep        stages. However, the occurrence of episodes during the sleep        state may be erroneously classified as awakening and terminate        stimulation (thereby reducing stimulation efficiency).    -   Balanced wake/sleeping state detection: The data analysis        algorithm can be configured for balanced detection of the awake        and sleeping states by implementing a balance between        specificity and sensitivity. This configuration is intended to        accommodate sufficient subject comfort but still provide        adequate stimulation length.    -   Sleeping state detection: The data analysis algorithm can be        configured for optimal detection of the sleeping state by        constraining the specificity to 0.9 and maximizing sensitivity.        This configuration may for example maximize stimulation        efficiency by preventing the occurrence of respiratory episodes.

However, awaking episodes may be erroneously classified as asleep andcontinue stimulation (thereby reducing subject comfort).

Model 1—Fixed Cut-Offs

In a first model, the cut-offs for optimizing the detection ofsleep/wake states have been selected irrespective of interindividualdifferences. A single optimal cut-off has been applied across patients.The cut-off configuration parameters are shown in FIG. 18 .

The cut-off data selection is discussed with reference to FIG. 19-21 .Specifically, FIG. 19 shows a Table with the data analysis algorithmconfigured for wake state detection, which results in a difference intotal sleep time (TST) of 45% and a stimulation duration <4 h in 50% ofsubjects. FIG. 20 shows a Table with the data analysis algorithmconfigured for balanced wake/sleeping state detection, which results ina difference in TST of ^(˜)15% and a stimulation duration <4 h in 6.5%of subjects. FIG. 21 shows a Table with the data analysis algorithmconfigured for sleeping state detection, which results in a differencein TST of ^(˜)7% and a stimulation duration <4 h in 0% of subjects.

Model 2—Personalised Cut-Offs

In a second model, the cut-offs for optimizing the detection ofsleep/wake states have been selected individually for each subject,hence personalizing the sleep/wake detection to their own sleepingprofile. A different optimal cut-off has been applied to every subject.The cut-off configuration parameters are shown in FIG. 22 .

The cut-off data selection is discussed with reference to FIG. 23-25 .Specifically, FIG. 23 shows a Table with the data analysis algorithmconfigured for wake state detection, which results in a difference intotal sleep time (TST) of ^(˜)44% and a stimulation duration <4 h in43.5% of subjects. FIG. 24 shows a Table with the data analysisalgorithm configured for balanced wake/sleeping state detection, whichresults in a difference in TST of ^(˜)15% and a stimulation duration <4h in 0% of subjects. FIG. 25 shows a Table with the data analysisalgorithm configured for sleeping state detection, which results in adifference in TST of ^(˜)4.5% and a stimulation duration <4 h in 0% ofsubjects.

CONCLUSIONS

Based on the above presented results, it appears that a personalizedoptimization of sleep/wake detection cut-offs for the detection of sleepmay provide better results both in terms of sleep and wakeidentification. This procedure leads to a variability in total sleeptime (TST) that is inferior to 4.5% of the TST from the reference chinsensor. Bland-Altman analysis revealed a relatively tight distributionof the differences, with a systematic bias that is close to 0.

For comparison purposes, the analysis presents 3 Bland-Altman graphs ofthe following paired variables:

-   -   FIG. 26 shows a comparison of chin sensor data with the cheek        sensor data.    -   FIG. 27 shows a comparison of the chin sensor data with the        sleep/wake detection rule based on standard deviations (SD) of        the cheek sensor data.    -   FIG. 28 shows a comparison of the chin sensor data with the        sleep/wake detection rule based on maximum values (MAX) of the        cheek sensor data.

Altogether, these data suggest that it is possible to detect sleep/wakephases with a MM recording device incorporated in the wearable deviceand mounted near the stimulation zone. The primary objective of thedevice would be to detect sleep and wake phases in order to activelypilot the stimulator so that the stimulation is initiated when thepatient falls asleep, and the stimulation is terminated when the patientwakes up.

DISCUSSION

To reduce the computational complexity for the algorithmic analysis, itwas envisaged to extract simple features from MM signals (standarddeviation, maximum values, minimum values, mean, median, etc.) for each30 seconds epoch of the signal and apply simple formulas to bestclassify cheek-derived MM signal into wake and sleep labels as definedby the reference chin-derived MM signal.

It appeared that standard deviation and maximum values were the mostdiscriminative for detecting sleep/wake labels. To optimise thedetection thresholds 3 different scenarios can be contemplated:

-   1. Maximization of wake detection and erroneous detection some sleep    episodes as quiet wake (the stimulation will only start when the    patient is obviously asleep, hence restraining the time window when    the treatment is active). This scenario favours comfort by    minimizing stimulation time while awake.-   2. Balanced detection of wake and sleep, ensuring that most    stimulation is restricted to true sleep and that stimulation lasts    for the most part of the sleep period.-   3. Maximization of sleep detection and erroneous detection of quiet    wake as sleep (the stimulation could start when the patient is    quietly awake, potentially disrupting the transition from wake to    sleep). This scenario favours treatment efficacy by maximizing    stimulation time.

In view of the reviewed data, it would appear the 3^(rd) scenario (sleepoptimization) is preferred for the following reasons:

-   -   TST differences between the cheek and the chin MM sensor are no        greater than what is expected from interscorer variability        (^(˜)85%).    -   Application of simple detection rules to cheek-derived MM        features allowed for detection of sleep and wake states        with >75% accuracy, as initially hypothesized.    -   Scenario 3 leads to difference in TST of ^(˜)4.5% and a        stimulation duration shorter than 4 h in 0% of subjects (4 h of        daily treatment for OSA being recommended in clinical practice).

Implementation

Given these data, the following recommendations may be formulated forimplementation in the wearable device's functionality:

-   1. The stimulators can have 2 different modes for being activated: a    manual mode where users can decide when the stimulation starts and    an intelligent mode where stimulation starts depending on users' MM.-   2. The manual mode shall be programmable entirely:    -   a. Users shall be able to decide to start the stimulation        directly.    -   b. Users shall be able to decide to start the stimulation with a        delay (e.g., the stimulation will start 20 minutes after        initiation).    -   c. Users shall be able to decide to start the stimulation with a        progressive ramp to reach optimal current intensity.-   3. The intelligent mode functions as follows:    -   a. The MM signals will be processed by 30-seconds epochs in a        first intention. This time window shall be programmable.    -   b. Different features shall be extracted from the 30-seconds        epochs. The features shall be programmable. Standard deviation        and maximum values shall be extracted in a first intention.    -   c. The 30-seconds epochs shall be overlapping with a        programmable interval and not successive to ensure that users do        not have to wait 30 seconds for the stimulation to stop when it        is supposed to. The 30-seconds epochs shall be refreshed every        second as a first intention.    -   d. The intelligent stimulation mode will be implemented with the        fixed standard deviation and maximum value thresholds that have        the most sleep/wake discrimination value in the above-described        report for the selected scenario (i.e., optimal sleep        detection).        -   The selected thresholds are the following:            -   Wake is detected if standard deviation of gyroscope norm                >1.17.            -   Wake is detected if maximum value of the gyroscope norm                >14.35.    -   e. The pre-defined sleep/wake thresholds implemented in        intelligent stimulation mode shall be programmable and        personalized per patient. These thresholds shall be modified        based on a first stimulation night to optimize sleep or wake        detection in any given user. It shall be possible to use a first        night with fixed parameters to distinguish sleep/wake to extract        cut-off points adapted to each patient.-   4. The intelligent mode shall also be programmable:    -   a. Users shall be able to decide to start the intelligent        stimulation directly (i.e., sleep/wake detection with the        detection rules will start directly after initiation).    -   b. Users shall be able to decide to start the intelligent        stimulation with a delay (i.e., sleep/wake detection with the        detection rules will start 20 minutes after initiation).    -   c. Users shall be able to decide to start the intelligent        stimulation with a progressive ramp to reach optimal current        intensity (i.e., sleep/wake detection with the detection rules        will start after a programmable delay (in minutes) after        initiation and current will progressively increase to optimal        intensity).-   5. Following awakenings in both activation modes, stimulation will    resume after a programmable delay (in minutes) and the absence of    wake detection.

It is understood that the embodiments presented in present Example 6form preferred embodiments of the wearable device of the presentdisclosure.

What is claimed:
 1. A wearable device for decreasing respiratory effortof a subject during sleep, the wearable device comprising: a housingconfigured to be worn on the subject's head and/or neck during sleep; aleft bipolar electrode associated with the housing and configured to bemounted on the subject's skin to stimulate left tissue associated withthe subject's left masseter muscle; a right bipolar electrode associatedwith the housing and configured to be mounted on the subject's skin tostimulate right tissue associated with the subject's right massetermuscle; and a stimulator associated with the housing and coupled to theleft and right bipolar electrodes, the stimulator configured to causethe left bipolar electrode to transcutaneously stimulate the left tissueto cause the left masseter muscle to contract and to cause the rightbipolar electrode to transcutaneously stimulate the right tissue tocause the right masseter muscle to contract, thereby elevating thesubject's mandible to decrease respiratory effort during sleep.
 2. Thewearable device of claim 1, wherein the left and right bipolarelectrodes each comprise adhesive surfaces configured to be adhered tothe subject's skin.
 3. The wearable device of claim 1, wherein thehousing comprises a collar configured to be worn on the subject's neckduring sleep.
 4. The wearable device of claim 3, further comprising aleft cable extending between the left bipolar electrode and the collarand a right cable extending between the right bipolar electrode and thecollar.
 5. The wearable device of claim 1, wherein the stimulator isconfigured to cause the left bipolar electrode and the right bipolarelectrode to transcutaneously stimulate simultaneously.
 6. The wearabledevice of claim 1, wherein the housing comprises a polyester garment. 7.The wearable device of claim 1, wherein the housing comprises a batteryconfigured to supply power to the stimulator.
 8. The wearable device ofclaim 1, wherein the stimulator is programmed with a stimulation regimewherein the stimulator causes transcutaneous stimulation for astimulation period followed by no stimulation for a rest period, whereinthe stimulation period followed by the rest period is repeatedthroughout the subject's sleep.
 9. The wearable device of claim 8,wherein the stimulation period is 1 to 20 seconds and the rest period is1 to 20 seconds.
 10. The wearable device of claim 9, wherein thestimulation period is 5 seconds and the rest period is 5 seconds. 11.The wearable device of claim 1, further comprising a data linkconfigured to provide wireless connection.
 12. The wearable device ofclaim 1, further comprising a gyroscope configured to sense rotationalmovement of the subject's mandible.
 13. The wearable device of claim 12,wherein the stimulator is configured to cause transcutaneous stimulationresponsive to rotational movement of the subject's mandible sensed bythe gyroscope.
 14. The wearable device of claim 1, further comprising anaccelerometer configured to sense movement of the subject's mandible.15. The wearable device of claim 14, wherein the stimulator isconfigured to cause transcutaneous stimulation responsive to movement ofthe subject's mandible sensed by the accelerometer.
 16. The wearabledevice of claim 1, further comprising a gyroscope configured to senserotational movement of the subject's mandible and an accelerometerconfigured to sense movement of the subject's mandible.
 17. The wearabledevice of claim 1, wherein the stimulator is configured to causetranscutaneous stimulation in a biphasic and symmetric manner.
 18. Thewearable device of claim 1, wherein the stimulator is programmed tocause transcutaneous stimulation at a frequency selected from 30 to 50Hz.
 19. The wearable device of claim 1, wherein the stimulator isprogrammed to cause transcutaneous stimulation at a pulse width selectedfrom 225 μs to 275 μs.
 20. The wearable device of claim 1, wherein theleft bipolar electrode comprises a first, left electrically conductiveelement and a second, left electrically conductive element configured tohave the transcutaneous stimulation applied therebetween, and whereinthe right bipolar electrode comprises a first, right electricallyconductive element and a second, right electrically conductive elementconfigured to have the transcutaneous stimulation applied therebetween.21. The wearable device of claim 20, wherein the first, leftelectrically conductive element is configured to be mounted at the leftmasseter muscle's motor point and the second, left electricallyconductive element is configured to be mounted along a direction of theleft masseter muscle's fiber, and wherein the first, right electricallyconductive element is configured to be mounted at the right massetermuscle's motor point and the second, right electrically conductiveelement is configured to be mounted along a direction of the rightmasseter muscle's fiber.
 22. The wearable device of claim 1, furthercomprising a sensing unit configured to record mandibular movement ofthe subject and a processing unit operatively connected to the sensingunit, the processing unit configured to receive, from the sensing unit,mandibular activity data and to determine, from the mandibular activitydata, one or more mandibular features.
 23. The wearable device of claim22, wherein the sensing unit comprises a gyroscope and/or anaccelerometer configured to record mandibular movement.
 24. The wearabledevice of claim 22, wherein the sensing unit is mounted on the leftand/or right bipolar electrode.
 25. The wearable device of claim 22,wherein the processing unit comprises a respiratory effort and/or arespiratory disturbance detection module configured to detect anincrease in respiratory effort and/or occurrence of a respiratorydisturbance in the subject's mandibular activity data and to cause thestimulator to adjust one or more stimulation parameters and/orstimulation programs to reduce the respiratory effort and/or occurrenceof the respiratory disturbance.
 26. The wearable device of claim 22,wherein the processing unit comprises a muscle fatigue detection moduleconfigured to detect presence of muscle fatigue in the subject'smandibular activity data and to cause the stimulator to adjust one ormore stimulation parameters and/or stimulation programs to reduce themuscle fatigue.
 27. The wearable device of claim 22, wherein theprocessing unit comprises a sleeping stage determination moduleconfigured to determine a sleeping stage in the subject's mandibularactivity data and to cause the stimulator to adjust one or morestimulation parameters and/or stimulation programs when a change in thesleeping stage is determined.
 28. A method for decreasing respiratoryeffort of a subject during sleep, the method comprising: providing ahousing configured to be worn on the subject's head and/or neck duringsleep; transcutaneously stimulating, via a left electrode associatedwith the housing, left tissue associated with the subject's leftmasseter muscle to cause the left masseter muscle to contract; andtranscutaneously stimulating, via a right electrode associated with thehousing, right tissue associated with the subject's right massetermuscle to cause the right masseter muscle to contract, whereintranscutaneously stimulating the left and right tissue elevates thesubject's mandible to decrease respiratory effort during sleep.
 29. Awearable device for decreasing respiratory effort of a subject duringsleep, the wearable device comprising: a housing configured to be wornon the subject's head and/or neck during sleep; a left bipolar electrodeassociated with the housing and configured to be mounted on thesubject's skin to stimulate left tissue associated with the subject's atleast one left target muscle selected from a left masseter, a leftpterygoid, and/or a left temporalis muscle; a right bipolar electrodeassociated with the housing and configured to be mounted on thesubject's skin to stimulate right tissue associated with the subject'sat least one right target muscle selected from a right masseter, a rightpterygoid, and/or a right temporalis muscle; and a stimulator associatedwith the housing and coupled to the left and right bipolar electrodes,the stimulator configured to cause the left bipolar electrode totranscutaneously stimulate the left tissue to cause the at least oneleft target muscle to contract and to cause the right bipolar electrodeto transcutaneously stimulate the right tissue to cause the at least oneright target muscle to contract, thereby elevating the subject'smandible to decrease respiratory effort during sleep.
 30. A method fordecreasing respiratory effort of a subject during sleep, the methodcomprising: providing a housing configured to be worn on the subject'shead and/or neck during sleep; transcutaneously stimulating, via a leftelectrode associated with the housing, left tissue associated with atleast one left target muscle selected from a left masseter, a leftpterygoid, and/or a left temporalis muscle to cause the at least oneleft target muscle to contract; and transcutaneously stimulating, via aright electrode associated with the housing, right tissue associatedwith at least one right target muscle selected from a right masseter, aright pterygoid, and/or a right temporalis muscle to cause the at leastone right target muscle to contract, wherein transcutaneouslystimulating the left and right tissue elevates the subject's mandible todecrease respiratory effort during sleep.